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Exploring proteins in your body and beyond

2 structure to living things.1 2 Diameter of a hydrogen atom STRUCTURE AND MOVEMENT 4 4 are found in nature Prokaryotes (e. Size of proteins relative to other substances (proteins in GREEN) How many amino acids. All measurements in nanometres (nm).7 picked a focus protein for each. and they are used widely 14. and estimates can be 100 000 made using different methods and/or baseline data.0 UK 6. You can Are the figures recent? How might also download the PDF of this magazine and an organisation’s ‘agenda’ affect subscribe to the Big Picture series.html. curriculum links and eggs._ protparam1?Q8WZ42@1-34350@ Translation%3A_Protein_synthesis SIGNALLING How proteins are involved in cell signalling and communication 10 strength of different substances (PROTEINS IN GREEN) Mitochondrion 300 1900 finding data CATALYSIS How. including extra articles.9 our bodies.nih. arranged if a protein has more than one and cereals.wikibooks.0 Primary: The sequence of amino acids that makes up a 0. www. In this Quaternary: How different polypeptide chains are Total: 121.ucdavis.1371/journal. we explore proteins by their different functions and have Tertiary: The unique 3D shape that some proteins take.3 system and catalyse chemical 29. held Secondary: The shape that the chain of amino acids Bangladesh reactions. too – different sources might define ‘size’ ONLINE or ‘strength’ differently.7 Total: 46. how it calculates and presents data? Source: en. Total: 86. Find more resources at www. linked by peptide bonds. milk. Source: www.4 messages and molecules around protein or polypeptide chain. Tensile strength (the force required to pull apart a substance). held together by hydrogen bonds. web. together by interactions between amino acid side chains. data can be interpreted in different ways. Argentina wellcome.8 2. in industry and medicine 1500 Wool High-tensile steel Go to www.. Other country data available.8 20 Ribosome in human proteins from place to place Amino acid 10 8 DEFENCE AND SURVIVAL are essential for humans Amino acids per second How proteins keep us alive and well Source: biowiki.wellcome. measured in megapascals (MPa). All figures are in grams per capita per Why don’t they match? HIV Human egg Bird muscle 53 proteins for more teaching resources.4 proteins. carry The_Pathway_of_Gene_Expression/Chapter_14.. and they do all sorts of fish and seafood. Source: faostat3.5 takes.6 acids. as enzymes. 2009.? Speed of protein synthesis INSIDE 2 at least Humans 700 PROBING PROTEINS A numerical look at proteins 0. PROBING PROTEINS Dietary sources of protein by country A numerical look at all things protein Proteins are polymers of amino 1. bacteria) 20 15 How proteins give structure to organisms and help them move TRANSPORT How proteins carry substances 6 Globular protein 0. They give Levels of protein structure 3000 Source: www. Sources are meat.13 28.3 incredible things.9 3. useful web links. support the immune 19.mhhe.nlm.expasy.7 38. proteins 12 Carbon fibre catalyse reactions (man made) 4000 Spider silk Putting this diagram together.5 0.html. lesson 200 (man made) Which should you choose? The source itself is important – is it reliable? ideas.ncbi.g.0011234 2 | BIG PICTURE 19: PROTEINS SPRING 2014 | 3 . Definitions we Collagen triple helix found that different sources gave real voices Three people talk about their interest in proteins 14 100 different numbers for the same thing.

their make-up is very noticeable. including dragline (to attach the spider cells and their contents move. Meaty issues Danlos syndrome can also cause Discussing protein in the diet weakness in heart valves. In 2013. which fills genetic mutations can weaken the are constantly being built. There Proteins give our cells. cilia and flagella strong. which are then and hemp – contain all the pressure on cropland or simply expensive diversion from are usually fibrous.Structure and movement FAST FACT Spider silk is a strong. hair and feathers. so they come only crops ourselves. networks of microtubules inside the cell easily and heals badly. Others are composition as those found in essential amino acids from supplements or substitutes for raise livestock? have repeated sequences of amino acids. These form in the gaps between collagen growth and bones that break microtubules. be bundled Partially degraded collagen from ‘osteogenesis imperfecta’. and tryptophan. milk and Vegans do not eat anything most energy-efficient factory Questions Some of these problems arise Proteins can be separated into broad groups cheese contain proteins with derived from animals. and any variation in evolved to work in a range of different proline and X is usually a modified form of collagen. Brittle bone disease. thin rods that protrude from then wind round one another to form a example. tendons. The global appetite for it is meat substitutes made from a them together. as protein. Motile cilia and flagella are powered by tissue. this to hydroxylysine – also depend on are in short supply in our diet. the bones and skin of animals from mutations in one type of cilia can move fluid themselves instead prokaryotic cells such as bacteria. of some proteins).uk/motm/spider/page2. of protein for many people includes saturated fat as well eat insects regularly. Pro is often the protein in vertebrates is amounts.bris. pressure on food production: the first burger grown from video at www. Structural the outside. tissues and organs structure.wellcome. Altogether. ease promising innovation or an proteins. Many of the symptoms we can make some of them growing. humans cannot feeding crops to animals is cow stem cells was cooked and bigpicture/proteins. As such. that alter some amino acids these proteins down into foods – including soya. including collagen and keratin. People with Ehlers–Danlos Flagella. Digestion breaks other food sources. hundreds of times. Structural proteins such as polymers of the protein tubulin). see the Globular proteins include haemoglobin. ligaments and cartilage. Protein powder made their 3D structure has the hydrophobic the skin. naturally occurring protein. which is the collagen (see ‘Real Voices’ on pages of just being moved by it. modification. They help organisms. are bundles of species have microtubule. the proportions we need to Meat is an important source especially to red meat. You can already buy you? Why? arrays. The sequence is Gly. the flagellum common protein structure in the body. substance that gives marshmallows 14–15 for more on this). Read more about these on process called post-translational available for reuse in roughly essential amino acids. They tend to be soluble in water because capillaries cause bleeding under make ten so-called ‘essential’ much less efficient than eating eaten. • Can you list three pros and directly from changes in collagen broadly the same amino acid means they have to get The search is on for three cons of using land to Fibrous proteins form long fibres and often (water-hating) parts facing the centre and protein sequences. This amino Collagen fibrils combine There are more than 30 different cytoskeleton. such as proline to hydroxyproline or lysine If particular amino acids around the world (see page 3). such as bones. which is putting more protein-rich fungus. Motile these proteins are ‘highly conserved’. Some plant meat that could help humans • Are lab-grown burgers a They are insoluble in water. which is also caused by arranged bundles of antibodies in mammals and most enzymes. Molecular motors like this a range of different mutations. others Cilia. removing inhaled dust and flagellin. around one-third of all collagen are made in large Microtubules are very versatile and have Pro-X. They from proteins. protein has four polypeptide 4 | BIG PICTURE 19: PROTEINS SPRING 2014 | 5 . Cilia of the bronchus of the respiratory tract. which • Billions of people already beaks. Leaky However.wellcome. are also tightly tiny cellular machines.chm. a amino acids. Alterations to some other into the throat. and amino acids. calcium phosphate crystals can cause problems such as slow the surface of cells. which farming of meat. weakness in the walls of the bladder or uterus. offer healthier alternatives – feeding the world? tough parts of organisms. where Gly is glycine. Source: www. skin. pulled apart alpha helix seen in the secondary structure the space between cells in different structures supported by collagen. Conjugated proteins are those that Those enzymes – that convert build new proteins. acid sequence allows the polypeptide chain with other materials in the genes for collagen in humans. For example. and Microtubule structures are dynamic and to fold into a helix (this is different from the extracellular matrix. and secondary structures. from our diet. may help cells move and can also be involved in move muscles. arranged around a (non-protein) haem of scurvy (vitamin C deficiency) are from other molecules we eat. Three collagen helices ways in different tissues. in turn. Essential amino the least energy-efficient plant be a protein source of acids include phenylalanine food uses around one-tenth the future. shift cargo along DISCUSS have very stretchy skin that bruises sensing the environment outside the cell. an internal scaffold in cells. and sweets their squishy texture. which are larger. In bone.htm Focus protein: collagen Important On the move Keeping animals in shape connections Proteins keep cells together Collagen mutations cause disorders Smaller structures inside cells are often Wellcome Images Collagen comes in different varieties. teeth come loose. easily. For example. are seven types. In the human form. The most basic cilia move in proteins with very similar sequences helices covalently bond with each other to fibres to harden it. the walls of forms of collagen affect connective dead cells. quinoa to avoid eating animals. Ehlers– Eukaryotes (cells with nuclei) from any and organise chromosomes for cell division. Would Structural proteins knit together in stable include non-protein parts. from farmed insects could also wounds no longer heal. and rebuilt. microtubules form the proline called hydroxyproline. to the web) and swathing (for wrapping prey). fish. for Some mutations are fatal. create fibrils. as many fossil fuels as the Shutterstock/Elnavegante MORE ONLINE: www. For more on this topic. In into collagen fibres. or the ebb and flow of fluid outside the cell. claws. power cilia. which do The collagen triple helix is the most makes gelatine. which can. Millions of cilia not have a nuclear membrane. each vitamin C. and one of the thin they all have the same basic structure: a layers of the cornea that made of microtubules (tube-shaped sequence of three amino acids repeated protects our eyes. What’s your type? Meat. the hydrophilic (water-loving) parts facing caused by changes in the enzymes our bodies. but arteries. stable collagen triple helix. with lots of cross-links to hold haemoglobin. They are found in the membranes. which are also made syndrome. arises sensing changes in the environment. pages 7 and 10–11. and floppy Some proteins exist within cell after the basic protein is made. group (read more on page 6). move to sweep mucus up out of the lungs is made from a different protein called It is found in bones and teeth. seen in connective tissue.

sticking out on both sides. the globin Horse haemoglobin was the has no cure. a phenylalanine. have this life-shortening condition. Large protein of proteins known as G-protein-coupled with a microscope they arrangement of atoms complexes and ribosomes receptors. Other side of the membrane. transfer oxygen: it contains These float freely in the blood a handful of patients who sportspeople want to use is involved in many things. even if meant that. This allows blood to carry 70 times the protein and blood its dark protein. and protein. This basic system is very versatile and blood does a lot more than polymers of the globin subunits. These share a similar basic are too small to transfer the chemical energy from food to surrounding the lungs. holds the key to its function. white cells. but this religious beliefs forbid it). also probed with nuclear Shutterstock/Sebastian Kaulitzki MORE ONLINE: www. and About half of all drugs used in medicine act are part of the immune are broken down. but sometimes there isn’t to create oxygen carriers for using haemoglobin from • Should doctors give patients seven times. we may be able specific molecule. donation ( and several owe on G-protein-coupled receptors. Iron gives conditions caused by a defective transport acids) and almost 2000 different genetic proteins that control the traffic across them. which normal haemoglobin until they blood transfusions. Take these proteins a very common secondary structure. atoms. This removes a membrane itself is made of phospholipid. Jehovah’s this be allowed? from hormones and neurotransmitters. stable. The alpha helix. not all do some of the work. or The altered protein does not fold properly and hydrophilic (water-loving) ones at each between amino acid atoms. No artificial • Should doctors transfuse This causes a change in shape that leads to a defined structure and problem that took many is still a tough problem the binding and activation of a previously Helping patients survive with the USA. which which accounts for two-thirds of all cases and hard to study. binds oxygen in muscle The protein involved – the cystic fibrosis is the 508th amino acid in the sequence. a globular shift and ‘grab hold’ of any Our cells have an outside and an 6 | BIG PICTURE 19: PROTEINS SPRING 2014 | 7 . however. The most common. of spots that is recorded on when purified. that anyone can play (fold. directions. in second protein for which scientists often have repeated chest infections and bases in the CFTR protein. The chain has stretches of alpha helix. chemicals such as adenosine triphosphate (ATP) are found in the mitochondria of our Solving structures cells (see pages 12–13). The first. lungs and specific molecules. The other three then in your blood. red colour. The that makes a particular can be seen using electron sequence. raise the risk of a heart attack. Many CFTR – was named after the condition. they haemoglobin interact. is a deletion of three DNA membrane. single amino acid.g. because their cells and modifying it to keep it coating and making new blood need it? confirmed that they had atoms. presented a harder acid sequence. Whole haemoglobin treated to make carriers are in regular use. which crosses the membrane Blood transfusions save lives. passing oxygen. change in the composition of sweat and of membrane but don’t work as they should. One day. use chemical energy to move molecules structure. and clotting factors may increase blood pressure and transfusions. the Cystic fibrosis is one of the most common The CFTR protein is large (1480 amino are divided by membranes studded with iron atom cradled in a ring of four nitrogen process is reversed.wellcome. When you shine a beam of intense X-ray sources and Computer programmes taste and smell. Hemopure. improved computational have been developed to in clotting. myoglobin. Many straddle the Like many globular proteins.wellcome. but just one amino acid chain. going on outside the cell and pass a signal site. (water-hating) amino acids in the middle hydrogen bonds and van der Waals forces tissue and has a very similar structure transmembrane conductance regulator. plants and even bacteria. although they Witnesses do not accept blood molecules splits and proteins crystallise readily. which membrane proteins fold to put hydrophobic under the influence of electrostatic bonds. mutations produce proteins that are out of the membrane and they tend to more tightly wound than the triple helix of proteins have been sequenced – in A faulty version of the protein causes a too short or that are present in the cell unravel. them along by incorporating Prize in Chemistry for 2012 was awarded for in the plasma. the regular array of protein methods. In the tissues more compartments within. enough in the blood bank blood. in theory. but are each tailored to a shapes of proteins was the straightforward. giving a pattern in particular. but they have been given to • Why might some by X-ray crystallography. and passing on the messages platelets. the maths is good for studying proteins Researchers are exploring a large group they look like. Proteins. The Nobel diverts the beam in many Transmembrane proteins. People who are affected of cystic fibrosis. their years to solve. be solved using more is astronomically large. animals. a detector. that subunit changes bigpicture/proteins). Source: mentalfloss. Some are pumps. It and so is broken down by the cell. their lives to these substitutes. Is synthetic blood a reality? fully we need to see what not a protein). their parents forbid it? inactive protein – a G protein – inside the structures could be solved big structures can often number of possible shapes cell. Current efforts involve outdated human blood blood against their will and discovery that pure proteins with their thousands or to predict how a protein or a patient won’t accept the removing haemoglobin from red encapsulated in an artificial without consent if they The receptor reads an outside signal. Haemoglobin. The complexes only DISCUSS Why do scientists study proteins’ shapes? work when embedded in the membrane because they set up an electrochemical Building Blood To understand proteins such as diamond (which is magnetic resonance. is a preparation of cow haemoglobin-based oxygen children if necessary. Protein structures are it/portal/) – try it! For simple crystals. but even needed to calculate the in solution. developed in from stem cells. including sight. Huge enzyme complexes that oxygen molecule in the blood capillaries online (www. Around 9000 people in the UK mutations are known. is forms of haemoglobin and related regulates the movement of chloride ions. channels for The way that the four subunits of Comparing the sequences indicates mucus secretions in the throat. This even tens of thousands of folds from its amino usually a molecule that binds to the protein. an that need the oxygen. so which the protein chain coils around itself solved the 3D structure. see our animation to the which are important and work more or less like would not normally accept blood substitutes? Should X-rays through a crystal. which across the membrane. Membrane-bound proteins are numerous as much oxygen as blood plasma alone. contains special oxygen carriers. These spaces Each protein contains four haem groups. which gradient across it. that also responds to low temperatures. Some sense what is subunits each contain one oxygen-binding first evolved billions of years ago. are unstable them into a computer game research on these proteins. its quaternary that they all descended from a intestines. can be crystallised. to solve because the substitutes is tricky. Researchers are trying Other approaches include Questions: key to ‘seeing’ the complex X-ray pattern is relatively microscopy. Today.Transport FAST FACT Mint-flavoured things taste cold because the menthol Proteins carry substances around our bodies and act as gatekeepers to in mint causes the activation of an ion channel protein control what goes in and what comes out of cells. scientists have tried to help system. Four single ancestral globin Focus protein: haemoglobin Cellular signals Carries oxygen around the body Channelling failure Membrane receptors are A protein problem causes cystic fibrosis important proteins Oxygen moves out of your lungs dissolved shape. problems with their digestive system. collagen. Some proteins are pores. When the first iron atom takes up an For more.

a protein does not work fatal Creutzfeldt-Jakob Parkinson’s and Alzheimer’s Questions: mouse lymphocytes with cancer proteins indicate something is Poisonous snakes often harm their properly. But proteins fold properly gets • How are doctors using low different shapes. tion of the enzyme thrombin from When folding goes awry. A collection of soluble which the protein will prion: prion proteins are what is called variant CJD. In vital for keeping organisms alive. They are often it. other prions and induces are caused by misfolded the hope that one day medicine will be the cells to grow. for ways to block outside agents same four-chain structure – two heavy type of antibody. For example. antibody response. MORE ONLINE: 8 | BIG PICTURE 19: PROTEINS SPRING 2014 | 9 . of the prion collects with and Huntington’s disease just their heads – frozen after death. their amino acid sequence.ncbi. which cause A new protein has to find to a diseased form inside the machinery that helps practice became routine? be produced with endlessly MAbs that block cell–surface blood to coagulate inside the blood the right shape among the patient’s body. If an antibody transport proteins and enzymes The main culprit is an enzyme Antigens are molecules that can provoke encounters an antigen that matches as well as attacking cell that attacks the lining of the an immune response. together and cannot be to life. Bee venom delivers a dose Asthma attacks. which ‘stickier’ than the desired from cows with bovine cancers. which can Other medical uses include thrombin-like enzymes. they can give MAbs are also used in its precursor protein prothrombin. either • Would you want your body to be frozen cells that grow indefinitely. virus). acid strings in which a threonine side itself relies on the precise end product and begin spongiform encephalopathy chain has a sugar molecule attached. Snakes produce more than 100 that eventually kills cells. a 26-amino-acid are often triggered by proteins Louise Murray/Science Photo Library binding sites. Such natural antifreeze molecules proteins is activated when tissue is keep if it finds it. such as after a prey by interfering with blood clot. The antibody’s four can make as many as a wasp stings and snake bites. to accumulated ‘junk’ arises when a prion protein because the protein clumps after you die? Why? hybrid cells yield monoclonal heart attack. for bleed for long. or ‘mad cow disease’).) to locate target molecules under of breast cancer and inhibits between the unfolded chain species. temperatures? (Hint: start exploring Antibodies tagged with Herceptin (trastuzumab) blocks of possibilities. A famous example is the some people developed small to cause damage. from our immune system. and include parts of bacteria.g. Any One of blood’s amazing properties is folding of the protein to clump together before (BSE. Some of transmitted between people this by searching for “therapeutic fluorescent dye enable scientists a receptor found in some types the intermediate shapes or even between different hypothermia” online. in of antibody. They could Antibodies are made by white you whether cells in a tissue are When you cut yourself. Researchers pregnancy test kits to detect Thrombin. Starting in the mid-1990s.wellcome. which leads to the activa. the antigens will be HIV (human immunodeficiency developing in those exposed antigens’. which do not usually trigger an destroyed by the immune system. converts the soluble Having the wrong shape diseased form too. Shutterstock/Ilya Andriyanov this natural antifreeze and remain too starts the repair of blood vessels if they that has the lowest energy. in turn. At the hundred million antibodies. as in the disposed of normally. spring a leak. lungs. the results are usually bad. end of the antibody arms are the antigen. as precisely as an enzyme binds to Researchers in the USA are designed to block the enzyme viruses and cells from transplanted blood its substrate. receptors. as discovered when the microscope. a peptide that that it contains a liquid toolkit that chain(s). A drug in development is proteins. which means a hundred of for instance. DISCUSS Focus protein: immunoglobulin Under attack Binding to unwanted invaders Scientists work to counteract some proteins’ effects Freeze! Antibodies or immunoglobulins (Ig for Each B lymphocyte Proteins and peptides can be Researchers are also looking Proteins stop fish from freezing short) are globular proteins. an astronomical number prion disease can also be less good at its job. ice crystals that form become coated with Bee venom delivers a dose of melittin. We in venoms such as bee and that trigger an overreaction and two light chains. This means that they Fish in the Antarctic live in salt water that cannot get close to human cells can be below normal freezing point. If you can induce cell the protein is found. A would increase and the fishes’ cells would Stemming the flow similar melittin-based system burst. you do not from chaperone proteins to This switch is irreversible variant CJD. The toxin is loaded into to the protein. may simply mean that Sometimes.Defence and survival FAST FACT Up to 85 per cent of people with asthma are allergic to house dust From antibodies to blood-clotting factors. There is one shape folding is complete. hybridising (joining together) conditions where particular which builds the scaffolding for a clot. where people blood cells called B lymphocytes. which have molecular ‘bumpers’ attached. in its normal shape switches grow larger or because • What would be the consequences if this antibodies (MAbs). A cascade of reactions is undo any misfolding as it because the diseased form Alzheimer’s. Others can lead disease (CJD). even be applied in cryonics. Source: www. which is the easily. them to convert to the proteins that clump sufficiently advanced to bring them back you pure antibodies. chains are arranged in a Y shape. the defect develop with age. and even where in the triggered. If the Part of the fold but can fuse with HIV particles. Parkinson’s pay to have their bodies – or sometimes Each cell produces just one kind example. Once they are tagged hoping to use melittin to destroy action and could prevent asthma or organs. The amiss. happens. five deaths donated organs have to be shipped for beginning of a blood clot. so they protect themselves from the Proteins are vital for blood clotting Everything a protein does and the working protein are people ate beef products could also have uses in treating cold with special glycopeptides – amino depends on its shape. variable regions that differ in million different amino acid peptide that inhibits several found in dust mite excrement. making a specific protein. in sperm banks or when an insoluble complex. each with the produces a specific used for attack – for example. Your own cells carry ‘self. although not membranes. But that harmless in their normally thought to be transmitted Using antibodies could help to improve tissue preservation damaged.nlm. it will bind to it. by antibodies. carefully tailored nanoparticles. ting. in the UK were caused by transplant in another hospital). combinations. Some newly made to make a super-stable meat. first did this 35 years ago by hormones and to help diagnose protein fibrinogen into insoluble fibrin. proteins are mites. This can tell tumour growth. water inside the fish froze then its volume Correct protein folding is essential which are much smaller. the drug vessels. protein chains need help complex that clogs cells. inhibits some proteins.nih. These proteins unite to make does not always happen folded state but can refold by prions in the affected Exploring antibodies as medicine and in research in medicine (e.

transporter proteins in the gut for several acceptable height. hormones and pheromones – herbivores. DISCUSS Feeling stuffed Hormones influence our eating Man the pumps Drugs can overcome mutations GROWING UP Pass it on Peptide hormones play an important part in bringing on both the pangs of hunger in proteins We all need growth hormone – but in the right amounts Pheromones get the message across and the feeling of being comfortably full after a meal. arranged in have lost some degree involved. but they will need to be tested discovered in the 1920s. the potassium might prevent obesity. To – cancer. Shutterstock / Irin-k Signalling FAST FACT When tomato plants are wounded or attacked by Proteins – as cell receptors. It has also been central the small. it promotes bone growth. Most Questions aid to conjugation (when bacterial cells release of insulin. Several chemicals that signals how much of the sugar glucose free by enzymes. It of response to insulin. Children who hormone? Who should decide? an index of the local population density. fat-soluble molecules that European Union. which stimulates inside a cell when the hormone binds though it is not licensed for this kind of as pheromone messengers because they can potassium ion channel that affected cravings for high-calorie foods when it is to a receptor on the outside of the use in the UK. even Insects often use small. for helps the molecule fold into the right shape. Like insulin and other hormone. the BRAF protein melanoma is often associated begins life as a much larger protein. Both of these hormones are now • What are the arguments for and creatures will make a glowing chemical only made by genetically engineered bacteria. growth themselves with human growth way if enough bacteria are nearby. This system binds. left to a single hormone. and for hormone has many other metabolic hormone to slow down ageing? example.nih.ncbi. often appears in later life. The skin cancer two chains linked by disulphide bonds. People with small amounts of a hormone contains the information to can also arise in individual human protein to be made in engineered type 2 diabetes. • What is an ‘acceptable height’ for link to transfer DNA). Protein usually requires a signal from with BRAF mutations. ghrelin can pass through cell membranes and (bovine somatropin) is used to boost are effective messengers in solution. a kinase. against the use of cow growth when individual bacteria have detected that Humans naturally produce less hormone in dairy farming? there are enough other bacteria nearby for growth hormone as they age. cell. volatile molecules babies was caused by mutations in a hormone ghrelin. the enzyme BRAF is an enzyme that to uncontrolled cell growth It has just 51 amino acids. Typically. which most to be amplified inside the make a protein called BRAF. enzymes. can lead division in tissues sensitive to it. Steroid hormones are In some countries outside of the Protein and peptide pheromones are much the pancreas. travel relatively long distances in the air. Pheromones carry proteins function incorrectly or not at that receptors in the gut. effects. where regular insulin injections used to treat For example. The mutations make it permanently inhibit BRAF show promise as there is in the blood. form of the disease are spared the the processing and absorption of food. milk production in cows. The same types of chemicals tend to how these proteins function. is snipped Hormone systems often act kinases regulate many outside the cell. However. smaller. chemical group (a phosphate) be active. It was make too little or no insulin inside the cell. be used in hospitals. closely related protein made in the pituitary gland ageing. they release an 18-amino-acid polypeptide are central to communication in living things. However. some example. for 10 | BIG PICTURE 19: PROTEINS SPRING 2014 | 11 . and drugs often work by affecting to taste receptors. the secretion of insulin from cells in released in the gut. Some the emitted light to be visible. and several and too little or too much of it leads children who require human growth concentration of particular pheromones as which means that children with this other messengers in the gut influence to extremes of stature. Some people go as far as be involved. cells later in life. of specific food chemicals and trigger or bloodstream. which is released ageing or to boost their fitness. to the history of protein research. Research suggests Growth hormone is a small soluble people think growth hormone can delay in the same organism. that diabetes in some newborn One key messenger is the peptide a ‘second messenger’. and many use the The drug can be given as a tablet. either to slow the latter most often as receptors. BRAF cause growth disorders. and it was quickly People with type 1 diabetes cell to activate the enzyme protein kinase when insulin Some inborn mutations in in clinical trials before they can used to treat patients with diabetes. and some anti-ageing products messages between individuals of the same all. researchers found a drug that can combating inflammation in the gut. and is Growth hormone stimulates cell Bacteria release pheromones as an close the channels and trigger the implicated in our response to stress. don’t make enough growth hormone • What are the potential benefits This is useful in quorum sensing. Like insulin. Shutterstock/Valertyn Volkov MORE ONLINE: www. register the presence in the brain and released into the such as face creams now include growth species. even vaccinating against it. even without potential cancer treatments. adds a small regulates cell growth. It was protein free to do its job. and each kind can affect the other. called systemin into their circulation. but their role in appetite is not Hormones carry messages between cells Diseases can occur when membrane completely understood. which Their treatment initially onto another protein. For example. receptor on the outside of the operates by turning on a this Focus protein: insulin SWITCHING SIGNALS Regulating glucose in the blood Kinase proteins control cell processes Insulin is a small protein hormone that proinsulin. Source: www. Blocking the action of cell membrane. which to be chemically synthesised and the first hormone. focuses on diet. where they In affected babies.nlm. researchers found suppress hormone release. and pass channels are stuck open. For different amino acids and peptides. active as a kinase. it works by triggering injecting the hormone. Then a large fragment of the precursor. a bacterium that lives in marine glucose. Food intake is too important to be obviously. cow growth hormone more common among bacteria. including peptides and proteins. leaving through a sequence in which interactions in cells. such as usually transmit their message directly. the hormone.wellcome. peptide hormones. the first and are treated with the allows a signal carried by BRAF is a human gene that Some mutations. but has other roles in the body. between cells. soluble hormone the hormone binds to its insulin receptor. This triggers the activation of genes for defence throughout the plant. the first protein to be sequenced. there are receptors and can be given more until they reach an and risks for someone injecting a colony of bacteria behaves in a particular diabetes.

needs a our stomach that degrade large molecules and destroy Some proteases are very specific and do released when the fuel burns was absorbed are used in industrial settings. This is why we need including thiamin. Closer apoptosis. The proteasome stops DISCUSS example is the bacterium Thermus discovered as part of cells’ response to proteases attacking everything in the cell by aquaticus. In eukaryotic organisms. such as trees or and rejoin DNA double helices. explaining how more gradual deterioration seen Eye of Science/Science Photo Library heat. These competitive inhibitors come from vitamins and make up part of of proteins consisting of a transmembrane can be hydrolysed to provide the Generally. and other organisms that survive in NASA showed it is also able to misfolded ones. Biofuels are fuels remains to be seen. are among typically suffer hair Focus protein: ATP synthase Cunning catalysts Capturing energy for our cells Enzymes are proteins Calling adenosine triphosphate (ATP) making enzyme rotates 150 Enzymes. like inorganic chemical catalysts. which rotate. or of enzymes contribute. conserved across organisms. completes the production the enzyme and bring on extreme conditions have been found. as mentioned on to be produced without competing with water bear (Milnesium tardigradum. from their component amino acids. the thrive in high temperatures. Several viruses. an enzyme that detoxifies Black-eyed beans are a good source of B vitamins. food production – and reduce carbon right) can withstand prolonged drying proteases operate happily in this fingers disappears). times a second. MORE ONLINE: www. are tagged with a small protein named the temperature of a hot cup of tea. NAD is an pump and two linked motors. niacin and riboflavin. The protease. mainly proteases. as it Enzymes are proteins that increase the rate of reactions. and some in a big protein out essential reactions. the enzyme’s active site. carbon neutral because the carbon dioxide • Describe three other ways that enzymes produces the amplification. and ATP the activation energy for the reaction. can make good drugs – and poisons. It also occurs in development protein products from larger precursor plants and crop waste would enable biofuel A microscopic animal called the denature enzymes. Substrate–enzyme binding often component called a cofactor to work. is produced in the same way. but do not react and instead block cofactors. which to home. using the woody parts of for food production? from Thermus aquaticus. heating and cooling to separate chains. iStock cross the membrane. found in bacteria and in the membranes This protein is fundamental depends on weak electrostatic forces and Some contain a metal atom held inside a of mitochondria and plant chloroplasts. which is widely used in help to stabilise animal species. is a complex about this unusual protein Life on the edge Break it down! not active enough. often impressive nanoscale machine – a complex thrown into reverse.g. but our digestive the webbing between a growing fetus’s page 10. The water bears special bags of enzymes called lysosomes for maintaining the structure prolamin. This involves the activation of instance. gradient. progeria. uses cycles of protein There is also a more drastic process of breaking down is digestion. the symptoms of one type of These ‘extremophiles’ need specially radiation of space. first isolated from the heat stress. Growing old too soon Enzymes are involved in ageing Enzymes that are inactive. down a concentration every day. A major cause of progeria 3D structure. Thermophiles repertoire of heat shock proteins – complex that floats free in the cell. chemicals in the liver. when there is large-scale cell loss (e. use some during the life of the plant. Understanding more adapted enzymes so they can carry survive thanks to an unusually large inside the cells. when polypeptides. Proteases. and In 2013 a team of X-ray in the development of treatment ageing. often by at least a competes with the enzymes that break down methanol into toxic products that million times that of the uncatalysed reaction. biofuel is Questions: The synthesis of new DNA. Enzymes recognise proteins the ones we eat. Many are chaperone ubiquitin. the potential impact laboratories to amplify small newly formed that are no longer required and tag them.methanol. it makes ATP. inadequate supplies of lamin. Patients ZMPSTE24. from the atmosphere relatively 12 | BIG PICTURE 19: PROTEINS SPRING 2014 | 13 . synthase an enzyme hardly does it justice. A person is easily disrupted by changes in acidity stable chemical structure. as including HIV and crystallographers solved its for progeria and also explain the Proteins are generally sensitive to withstand the freezing temperatures Cells make proteins. Insulin. but they must also exaggerated form of ageing. which cells and has an identical sequence in all We make proteins by breaking down Digestive enzymes are useful in dioxide emissions by being used in place of (PCR). Organic True. or of the cell nucleus. include methanoate. Most organisms produce containing them in a protein assembly. but that have a similar shape to the enzyme’s copper and zinc in our diet. which is found in all eukaryotic The polymerase chain reaction proteins. The kept at a pH triggered by various kinds of cell damage. such as haem in but the enzyme’s general mechanism is makes and recycles roughly (pH). driving an axle that turns the other and producing ATP in the process. a whole set of enzymes. joint transmembrane protein. However. out and is a psychrophile – it can acidic soup. • How should we decide how much land withstand high temperatures.wellcome. but the protein is an part is that these motors can be they speed them up enormously by lowering substrate. energy to pump protons against and they need the right conditions to do Many enzymes need a non-protein example of a cofactor. Apoptosis is more than food digestion. damaged or It is seen in children with is a defect in a protease that several mutations disable in normal ageing. their job. Its enzymes work normally at role in protecting other proteins. enzymes are globular proteins. Source: www. Researchers have discovered fossil fuels. known as coenzymes. derived Different forms of ATP synthase are an electrochemical gradient. kill most cells and the organism. As protons their body weight in ATP enzyme activity. and lots to produce liquid biofuel. well digested scalding hot springs of Yellowstone some of these. and they have a general The proteins destined for destruction Digestive enzymes can be useful Park. Experiments by dispose of the unwanted. bonds in protein. Progeria is a very rare usually die in their mid-teens. DNA polymerase enzyme that can contents are the structure inside a cell. One so named because they were first proteasome. structure may eventually help Meet nature’s extremophiles The proteins that dispose of proteins many contributors to human problems and heart disease. hydrolyse (break) the peptide cereal crops. to use for biofuels and how much to use answer was to use Taq polymerase low enough to cells can be sacrificed for the greater good of of their proteases to produce finished In theory. but in recent decades bacteria of the Antarctic. tolerate the high vacuum and intense some protein degradation happens in a fibrous protein that is vital of lamin from its precursor. then building new ones industry. the active site. Competitive inhibitors are molecules traces of metals such as iron.Catalysis FAST FACT Alcohol is sometimes given to patients with antifreeze (methanol) poisoning. The cleverest cannot make new reactions happen. magnesium. The axle driving the ATP. Heat denatures proteins and destroys cytochrome 450. This enzymes in bacteria that can digest wood on forests of large-scale biofuel production samples of DNA. one motor turns. for made from living matter. At its most efficient. from niacin (vitamin B3). self-digestion: programmed cell death. to living things.

I’m a junior in usually have stunted growth. Liz Carpenter. This changed the conductivity be busy because I’m taking a the body needs to attend to the happens if they don’t have a class train around 50 kg and then lose be the biggest chance I’ve ever had to and could be measured with lot of advanced classes. quickly and animal health. taking fracture before it can continue disabled toilet? What happens the last 2 kg over a couple of weeks perform on the international stage. so if you’re training to keep things quiet. We support the brightest fragile bones. education to the sensor. the inventor of a test to detect but I am now working in Are there any treatments? school. I’m from Wellcome Images Why pancreatic cancer? bowing of the arms and legs.real voices Read an extended version of some of these interviews at www. mainly because I’m only 4’ 8”. Going from being I’ve created a novel paper sensor biotechnology companies to living in London. so I turned to the Internet been given is to patent your and achieved a lot in my life – protein thinking that it’s going to to find out. the mesothelin more diseases. I have to think: how category (48 kg). of activities. travelling and grows back is very weak and So I do have to do a lot of more you lift.wellcome. Find out more at (images. subject to the following people could have the cancer sensor to detect cancer using I’ve had approximately 200 disabled people. ISSN 1745-7777. Education editor: Stephanie Sinclair Editor: Chrissie Giles Assistant editor: Kirsty Strawbridge Writers: Dani Bancroft. when my Find out more at training is what helps you build the misleading context. The future of science depends on the quality of an ohmmeter that measures important exams. I also want Owing to multiple fractures. are speaking. the Wellcome Trust survival. as that’s or medium. causing planning for even the simplest heavy then you’re training better. Wen Hwa 14 | BIG PICTURE 19: PROTEINS SPRING 2014 | 15 . I started when I was 11. Ron. I’m also There is no known cure. I hold a few British records I’m not funded [by British Weight Stephen Ham. Chrissie Giles. I’m going out for drinks with I’m in the lightest bodyweight and the application of research to improve bonded with the antibody and high school so have two years This happens because when friends. Pauline Newnham. PU-5689/23K/10–2013/JS MORE ONLINE: www. no indication when I’m going Chocolate is my weakness. but every single day I find trustee is The Wellcome Trust Limited. When I www.jackandraka. There are extraordinary improvements in human and was a coating on the paper. This year will you’re constantly fracturing. All images. includes public engagement. but I’m light for my What’s next for you? health. London NW1 Big Picture is © the Wellcome Trust 2013 close family friend passed away have? which is a curvature of the sure that people view disabled Do you eat lots of protein? and is licensed under Creative Commons from pancreatic cancer. but your body is only going to use the exception of images and illustrations. The Find out more at of my chair onto a pavement food. obstacles to learning by having mum was carrying me. economically. to grow. Usually girls in this The 2014 Commonwealth Games will and commercial interests. thing? legs and short body. funded and able to train twice a day Advisory board: Iraj Ali. If Which category are you in? new sports. It takes a lot It’s a genetic disorder that rods into the back. for England. Iona Twaddell Project manager: Rosie Cotter Graphic designer: James Stride Multimedia producer: Chris Chapman Jack Andraka Samantha Renke Hannah Powell Illustrators: Glen McBeth. This is an open access publication The heavier you are. and repeated until there I want to diagnose a variety have very low bone density and What’s the most difficult short everything: short arms. The thing I eat most of the content may unless otherwise stated of diagnosing the disease so a pancreas was can create a be reproduced free of charge in any format I’m a full-time wheelchair user. britishweightlifting. How did you start weightlifting? How often do you train? Paul Connell. can also be deformed. That can push on our people as integral to society. In the 14 years Wellcome Trust: We are a global charitable antibody and nanotubes. Kim Hatfield. 2711000 (whose registered office is at 215 Euston Road. for pancreatic. for my age category and for my Lifting] at the moment. but it’s not. support them and to correct is the reason I’m so small. I used to be a language teacher.brittlebone. Giles Newton. the reaction is quite hard – but I choose to do it. When might the test be marketing and PR. Emma Cresswell-Maynard. When I was in middle school. I’m Working in the lab and learning The Wellcome Trust is a charity registered to break: I’ve been tipped out not really bothered about junk in England and Wales. UK). but protein straight after accurately. single-walled carbon and uniformly so it can get muscle once you’ve broken it down in must be attributed as the original author and open access to journal articles was a baby I would fracture up training. Its sole from the scientists there. no.wellcome. David mesothelin. I’m quite eager to make www. Ian Graham. Robert and nothing’s happened to me. Alex What is brittle bone disease? often be rectified by putting How do people react? squeeze training in around work is a What’s the best advice you Usually we have scoliosis. made from ordinary filter get the strip made more quickly Curvature of the spine can to working full time and trying to Hannah Baker. 2012 has opened people’s eyes to medical humanities. nanotubes and an antibody to to clinical trials. even know what a pancreas a lot! The best advice I’ve heart and lungs. unless otherwise indicated. Jon Turney. the standard of female foundation dedicated to achieving dry. I’ve always been very positive weight training is to overload on Cartoon illustrations are © Glen McBeth. My height’s an advantage. Analysing everything I do men. fun part – just testing your but I’ve rolled over in bed and chocolate’! no. Helen English. ovarian and concept’ to a finished product the body and is also known telescopic rods in my legs to I also often get asked if weightlifting Is it a male-dominated sport? Sabrina Taner lung taken to increase bone density. was. Yes. short lifting has rocketed.wellcome. and I’ve competed full time as a classroom assistant at Jonathan Schofield How does your test work? Right now I’m in talks with busy! I’m 27 and currently (bisphosphonates) that can be internationally for Great Britain and a primary school. Stephen Curry. David paper. They actually weight. I dipped the filter than I imagined! as osteogenesis imperfecta. The statistics I idea before you speak about How does it affect you? in spite of the fact that I’ve had help them build massive muscles. Bret Syfert US high school student Actress and public Olympic weightlifter Publisher: Mark Henderson Head of Education and Learning: Hilary and scientist relations professional Leevers What do you do? hypothesis and seeing where it Teachers’ advisory board: Peter Anderson. I of diseases easily. I didn’t Read widely and brainstorm spine. Thomas Sorenson. which Most of the time. which means that and because we don’t live in so much. We are independent of both political pushed the nanotubes apart. constantly trying to put weight on. though. before college. Our breadth of support After mesothelin was applied to develop my sensor to test people with the condition and reducing all the risks.  making the test? like me can create and innovate. a protein biomarker longer to get from ‘proof of affects type I collagen in I’ve had done. a world that is designed for is complex carbohydrates. Ann Mills-Duggan. Louise Stubberfield. what’s going to help me put on conditions: content must be reproduced detected earlier when they the Internet. the so I’m working really hard and trying electrical resistance. A mistake a lot of people make when Attribution 2. a process of science is the most www. with found shocked me. Alison the team Three people tell us about the part proteins play in their lives. and I was it publicly. available? doing some acting – I’m quite but there are a few drugs weight category. I’m a high school student and leads you. my projects. Fabia Allen. let it What are you working on now? our skeleton so it causes us to the best shape for weightlifters is since. determined to find a better way who didn’t even know what imperfecta. so I work Kaur. at secondary I train about five times a week. Women didn’t compete in the paper into a mixture of the There is a lot of collagen in any bowing. Jaswinder pancreatic cancer.0 UK. myself thinking ‘I really want some company registered in England and Wales. If a 15-year-old I’ve got type III osteogenesis to battle a lot due to my health. Usually Olympics until 2000. am I going to get there? What class at 45 kg. researching science education today. There’s in the attribution. the title of the document must be specified What was the best part of and scientific knowledge so kids to a few times a week. content must not be used in a would have a better chance of you can do! We need to remove started in the just imagine what breaks in my life. Lydia Harriss. The new bone that if there is a flight of stairs? to compete. women out there who are outlifting minds in biomedical research and the then measured the conductivity. 210183. I’ve also got shock. Ross MacFarlane. What do you do? snapped my collarbone.

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