PROTEINS

What is Protein?
 Polymer built from amino
acids that provides cells with
their shape and structure
and performs most of their
activities.

 A biological macromolecule
containing at least 30 to 50
amino acids joined by
peptide bonds
 A protein molecule is made from a long chain of amino acids held by
covalent peptide bond.
 Proteins therefore referred as polypeptides, and their amino acid chains
are called polypeptide chains.
 In each type of protein, the amino acids are present in a unique order,
called the amino sequence, which is exactly the same from one molecule
of that protein to the next.
20 essential
amino acids
Amino Acid Monomers
Side chain (R group
Amino acids are organic
molecules with carboxyl and
amino groups  carbon

Amino acids differ in their

properties due to differing side
chains, called R groups
Projecting from the polypeptide backbone are the
amino acid side chains – the part of the amino acid
that is not involved in forming peptide bonds.

The side chain gives an amino acid its unique

properties: some are nonpolar and hydrophobic,
some are positively or negatively charged, some can
be chemically reactive and so on.
Figure 5.16a

Nonpolar side chains; hydrophobic

Side chain

Glycine Alanine Valine Leucine Isoleucine

(Gly or G) (Ala or A) (Val or V) (Leu or L) (Ile or I)

Methionine Phenylalanine Tryptophan Proline

(Met or M) (Phe or F) (Trp or W) (Pro or P)
Figure 5.16b
Polar side chains; hydrophilic

Serine Threonine Cysteine

(Ser or S) (Thr or T) (Cys or C)

Tyrosine Asparagine Glutamine

(Tyr or Y) (Asn or N) (Gln or Q)
Figure 5.16c

Electrically charged side chains; hydrophilic

Basic (positively charged)

Acidic (negatively charged)

Aspartic acid Glutamic acid Lysine Arginine Histidine

(Asp or D) (Glu or E) (Lys or K) (Arg or R) (His or H)
 Amino Acid Polymers
Amino acids are linked by peptide bonds
A polypeptide is a polymer of amino acids
Polypeptides range in length from a few to more than a
thousand monomers
Each polypeptide has a unique linear sequence of amino
acids, with a carboxyl end (C-terminus) and an amino end
(N-terminus)

© 2011 Pearson Education, Inc.

Figure 5.17

Peptide bond

New peptide
bond forming

Side
chains

Back-
bone

Amino end Peptide Carboxyl end

(N-terminus) bond (C-terminus)
Protein Structure and Function

A functional protein consists of one or more

polypeptides precisely twisted, folded, and coiled
into a unique shape
Figure 5.18

Groove

Groove

(a) A ribbon model (b) A space-filling model

 The sequence of amino acids determines a
protein’s three-dimensional structure
 A protein’s structure determines its function
Figure 5.19

Antibody protein Protein from flu virus

 Four Levels of Protein Structure
The primary structure of a protein is its unique sequence of
amino acids
Secondary structure, found in most proteins, consists of coils
and folds in the polypeptide chain
Tertiary structure is determined by interactions among
various side chains (R groups)
Quaternary structure results when a protein consists of
multiple polypeptide chains
  Primary structure, the sequence of
amino acids in a protein, is like the
order of letters in a long word
 Primary structure is determined by
inherited genetic information

© 2011 Pearson Education, Inc.

Figure 5.20a
Primary structure

Amino
acids

Amino end

Primary structure of transthyretin

Carboxyl end
 The coils and folds of secondary
structure result from hydrogen bonds
between repeating constituents of the
polypeptide backbone
 Typical secondary structures are a coil
called an  helix and a folded structure
called a  pleated sheet
Figure 5.20b

Secondary Tertiary Quaternary

structure structure structure

 helix

Hydrogen bond
 pleated sheet
 strand
Transthyretin
Hydrogen Transthyretin protein
bond polypeptide
Figure 5.20c
Secondary structure

 helix

Hydrogen bond
 pleated sheet

 strand, shown as a flat

arrow pointing toward
the carboxyl end

Hydrogen bond
 Tertiary structure is determined by interactions
between R groups, rather than interactions
between backbone constituents
 These interactions between R groups include
hydrogen bonds, ionic bonds, hydrophobic
interactions, and van der Waals interactions
 Strong covalent bonds called disulfide bridges
may reinforce the protein’s structure
Figure 5.20f

Hydrogen
bond
Hydrophobic
interactions and
van der Waals
interactions
Disulfide
bridge
Ionic bond

Polypeptide
backbone
Figure 5.20e

Tertiary structure

Transthyretin
polypeptide
Figure 5.20g

Quaternary structure

Transthyretin
protein
(four identical
polypeptides)
 Quaternary structure results when two or more
polypeptide chains form one macromolecule
 Collagen is a fibrous protein consisting of three
polypeptides coiled like a rope
 Hemoglobin is a globular protein consisting of
four polypeptides: two alpha and two beta chains
Figure 5.20h

Collagen
Figure 5.20i
Heme
Iron
 subunit

 subunit

 subunit

 subunit

Hemoglobin
Figure 5.20j
Sickle-Cell Disease: A Change in Primary
Structure
A slight change in primary structure can affect a protein’s
structure and ability to function
Sickle-cell disease, an inherited blood disorder, results
from a single amino acid substitution in the protein
hemoglobin
Figure 5.21

Primary Secondary Quaternary Red Blood

and Tertiary Function
Structure Structure Cell Shape
Structures

1 Normal Molecules do not

hemoglobin associate with one
Normal hemoglobin

2 another; each carries

3 oxygen.
4
5 
 subunit  10 m
6
7



1 Exposed Sickle-cell Molecules crystallize

hydrophobic hemoglobin into a fiber; capacity
Sickle-cell hemoglobin

2 region to carry oxygen is

3 reduced.
4
5 
6  10 m
7  subunit


 What Determines Protein Structure?
 In addition to primary structure, physical and
chemical conditions can affect structure
 Alterations in pH, salt concentration,
temperature, or other environmental factors can
cause a protein to unravel
 This loss of a protein’s native structure is called
denaturation
 A denatured protein is biologically inactive
Figure 5.22

tu

Normal protein Denatured protein

2.4.A2 Denaturation of proteins by heat or by deviation of pH from the optimum.

Denaturation of proteins
The three-dimensional conformation of proteins is stabilized by bonds or interactions
between R groups of amino acids within the molecule. Most of these bonds and interactions
are relatively weak and they can be disrupted or broken. This results in a change to the
conformation of the protein, which is called denaturation.

A denatured protein does not normally return to its former structure

– the denaturation is permanent. Soluble proteins often become
Heat can cause insoluble and form a precipitate.
denaturation:
vibrations within
the molecule
breaks Extremes of pH can cause denaturation:
intramolecular charges on R groups are changed,
bonds or breaking ionic bonds within the protein
interactions. or causing new ionic bonds to form.

http://upload.wikimedia.org/wikipedia/commons/2/22/Fried_egg%2C_sunny_side_up_%28black_background%29.PNG
2.4.A2 Denaturation of proteins by heat or by deviation of pH from the optimum.

Denaturation of proteins

The background image shows white smokers, a particular kind of hydrothermal vent which
produces very hot carbon dioxide gas. These vents can be found deep in oceans and
produce temperatures in excess of 100 °C, but life can still be found around them.

Thermophiles are organisms (often archea or eubacteria) that live in relatively hot conditions
(45 to122 °C). In order that they can survive their proteins are stable at the higher than
normal temperatures they experience.

https://en.wikipedia.org/wiki/File:Champagne_vent_white_smokers.jpg
 Protein Folding in the Cell
 It is hard to predict a protein’s structure from its
primary structure
 Most proteins probably go through several stages on
their way to a stable structure
 Chaperonins are protein molecules that assist the
proper folding of other proteins
 Diseases such as Alzheimer’s, Parkinson’s, and mad
cow disease are associated with misfolded proteins
Figure 5.23

Correctly
folded
protein
Polypeptide
Cap

Hollow
cylinder

Chaperonin Steps of Chaperonin 2 The cap attaches, causing 3 The cap comes
(fully assembled) Action: the cylinder to change off, and the
1 An unfolded poly- shape in such a way that properly folded
peptide enters the it creates a hydrophilic protein is
cylinder from environment for the released.
one end. folding of the polypeptide.
 Scientists use X-ray crystallography to
determine a protein’s structure
 Another method is nuclear magnetic resonance
(NMR) spectroscopy, which does not require
protein crystallization
 Bioinformatics uses computer programs to
predict protein structure from amino acid
sequences
Figure 5.24
EXPERIMENT
Diffracted
X-rays

X-ray
source X-ray
beam

Crystal Digital detector X-ray diffraction

pattern

RESULTS

RNA DNA

RNA
polymerase II
Proteins include a diversity of structures,
resulting in a wide range of functions

 Proteins account for more than 50% of the dry mass of

most cells
 Protein functions include structural support, storage,
transport, cellular communications, movement, and
defense against foreign substances
 Types of Proteins
Enzymatic proteins
Defensive Proteins
Storage proteins
Transport proteins
Hormonal proteins
Receptor proteins
Contractile and motor proteins
Structural
Figure 5.15a

Enzymatic proteins
Function: Selective acceleration of chemical reactions
Example: Digestive enzymes catalyze the hydrolysis
of bonds in food molecules.

Enzyme
Figure 5.15e

Defensive proteins
Function: Protection against disease
Example: Antibodies inactivate and help destroy
viruses and bacteria.

Antibodies

Virus Bacterium
Figure 5.15b

Storage proteins
Function: Storage of amino acids
Examples: Casein, the protein of milk, is the major
source of amino acids for baby mammals. Plants have
storage proteins in their seeds. Ovalbumin is the
protein of egg white, used as an amino acid source
for the developing embryo.

Ovalbumin Amino acids

for embryo
Figure 5.15f

Transport proteins
Function: Transport of substances
Examples: Hemoglobin, the iron-containing protein of
vertebrate blood, transports oxygen from the lungs to
other parts of the body. Other proteins transport
molecules across cell membranes.

Transport
protein

Cell membrane
Figure 5.15c

Hormonal proteins
Function: Coordination of an organism’s activities
Example: Insulin, a hormone secreted by the
pancreas, causes other tissues to take up glucose,
thus regulating blood sugar concentration

Insulin
High secreted Normal
blood sugar blood sugar
Figure 5.15g

Receptor proteins
Function: Response of cell to chemical stimuli
Example: Receptors built into the membrane of a
nerve cell detect signaling molecules released by
other nerve cells.

Receptor
Signaling protein
molecules
Figure 5.15d

Contractile and motor proteins

Function: Movement
Examples: Motor proteins are responsible for the
undulations of cilia and flagella. Actin and myosin
proteins are responsible for the contraction of
muscles.

Actin Myosin

Muscle tissue
100 m
Figure 5.15h

Structural proteins
Function: Support
Examples: Keratin is the protein of hair, horns,
feathers, and other skin appendages. Insects and
spiders use silk fibers to make their cocoons and webs,
respectively. Collagen and elastin proteins provide a
fibrous framework in animal connective tissues.

Collagen

Connective
tissue 60 m
 Enzymes are a type of protein that acts as
a catalyst to speed up chemical reactions
 Enzymes can perform their functions
repeatedly, functioning as workhorses that
carry out the processes of life
 ADDITIONAL
INFORMATION
7.3.U7 The sequence and number of amino acids in the polypeptide is the primary structure. AND 7.3.U8 The secondary structure is
the formation of alpha helices and beta pleated sheets stabilized by hydrogen bonding. AND 7.3.U9 The tertiary structure is the further
folding of the polypeptide stabilized by interactions between R groups. AND 7.3.U10 The quaternary structure exists in proteins with
more than one polypeptide chain.

The four levels of protein structure. The level a protein conforms to is determined by
it’s amino acid sequence.

(Polypeptide) • The chains of amino acids fold or turn • The polypeptide folds and • The interaction
• The order / sequence of the amino upon themselves coils to form a complex 3D between multiple
acids of which the protein is • Held together by hydrogen bonds shape polypeptides or
composed between (non-adjacent) amine (N-H) • Caused by interactions prosthetic groups
• Formed by covalent peptide bonds and carboxylic (C-O) groups between R groups (H-bonds, • A prosthetic group is
between adjacent amino acids • H-bonds provide a level of structural disulphide bridges, ionic an inorganic
• Controls all subsequent levels of stability bonds and hydrophilic / compound involved
structure • Fibrous proteins hydrophobic interactions) in a protein (e.g. the
• Tertiary structure may be heme group in
important for the function haemoglobin)
n.b. although you don’t need to be able to outline the different levels of (e.g. specificity of active site • Fibrous and
structure for knowing of them helps to understand the difference in enzymes) Globular proteins
between globular and fibrous proteins. This is though required • Globular proteins
knowledge for AHL (7.3.U7 to 7.3.U10)
2.4.U6 The amino acid sequence determines the three-dimensional conformation of a protein.

Proteins are commonly described as either being

fibrous or globular in nature.
Fibrous proteins have structural roles whereas globular proteins are functional
(active in a cell’s metabolism).

In globular proteins the hydrophobic R groups are folded into the core of the molecule, away
from the surrounding water molecules, this makes them soluble. In fibrous proteins the
hydrophobic R groups are exposed and therefore the molecule is insoluble.
2.4.U7 Living organisms synthesize many different proteins with a wide range of functions.

Usage of proteins Nothing can compare with the versatility of proteins. Their functionality
and usage in organisms is unrivalled.

Function Description Key examples

There are thousands of different enzymes to catalyse specific chemical
Catalysis Rubisco
reactions within the cell or outside it.
Actin and myosin together cause the muscle contractions used in
Muscle contraction
locomotion and transport around the body.
Tubulin is the subunit of microtubules that give animals cells their shape and
Cytoskeletons
pull on chromosomes during mitosis.
Fibrous proteins give tensile strength needed in skin, tendons, ligaments and
Tensile strengthening collagen
blood vessel walls.
Plasma proteins act as clotting factors that cause blood to turn from a liquid
Blood clotting
to a gel in wounds.
Transport of nutrients
Proteins in blood help transport oxygen, carbon dioxide, iron and lipids.
and gases

• Key examples are outlined in more detail.

• Although a key example spider silk is not mentioned above as the table refers to uses within the organism
2.4.U7 Living organisms synthesize many different proteins with a wide range of functions.

Usage of proteins Nothing can compare with the versatility of proteins. Their functionality
and usage in organisms is unrivalled.
Function Description Key examples
Membrane proteins cause adjacent animal cells to stick to each other within
Cell adhesion
tissues.
Membrane proteins are used for facilitated diffusion and active transport,
Membrane transport
and also for electron transport during cell respiration and photosynthesis.
Some such as insulin, FSH and LH are proteins, but hormones are chemically
Hormones Insulin
very diverse.
Binding sites in membranes and cytoplasm for hormones,
Receptors neurotransmitters, tastes and smells, and also receptors for light in the eye rhodopsin
and in plants.
Histones are associated with DNA in eukaryotes and help chromosomes to
Packing of DNA
condense during mitosis.
This is the most diverse group of proteins, as cells can make huge numbers
Immunity immunoglobulins
of different antibodies.

Biotechnologically has allowed us to use proteins in industry examples are:

• enzymes for removing stains in clothing detergent
• monoclonal antibodies for pregnancy tests
• insulin for treating diabetics
• Disease treatments
Genetically modified organisms are often used as to produce
proteins. This however is still a technically difficult and expensive
process.
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein functions.

Rubisco
• Full name ribulose bisphosphate carboxylase
• Enzyme - catalyses the reaction that fixes carbon dioxide
from the atmosphere
• Provides the source of carbon from which all carbon
compounds, required by living organisms, are produced.
• Found in high concentrations in leaves and algal cells

http://upload.wikimedia.org/wikipedia/commons/b/b0/Mint-leaves-2007.jpg
http://upload.wikimedia.org/wikipedia/commons/thumb/7/74/Rubisco.png/220px-Rubisco.png
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein functions.

Insulin
• A hormone – signals many cells (e.g. liver cells) to
absorb glucose and help reduce the glucose
concentration of the blood.
• Affected cells have receptor (proteins) on their surface
to which insulin can (reversibly) bind to.
• Secreted by β cells in the pancreas and transported by
the blood.

The pancreas of type I diabetics don’t produce sufficient

insulin therefore they must periodically inject synthetically
produced insulin to correct their blood sugar concentration.

https://en.wikipedia.org/wiki/File:Inzul%C3%ADn.jpg
http://www.biotopics.co.uk/as/insulinproteinstructure.html
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein functions.

immunoglobulins

• Also known as antibodies.

• Two antigen (a molecule on the pathogen which provokes an immune
response) binding sites - one on each ‘arm’
• Binding sites vary greatly between immunoglobulins (hypervariable) to enable
them to respond a huge range of pathogens.
• Other parts of the immunoglobulin molecule cause a response, e.g. acting as a
marker to phagocytes (which engulf the pathogen)

https://upload.wikimedia.org/wikipedia/commons/thumb/a/a9/Antibody_IgG2.png/320px-Antibody_IgG2.png
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein functions.

rhodopsin

• A pigment that absorbs light

• Membrane protein of rod cells of the retina (light sensitive region at the back of
the eye)
• Rhodopsin consists of the opsin polypeptide surrounding a retinal prosthetic
group
• retinal molecule absorbs a single photon of light -> changes shape -> change
to the opsin -> the rod cell sends a nerve impulse to the brain
• Even very low light intensities can be detected.

http://commons.wikimedia.org/wiki/File:Rhodopsin.jpg
https://en.wikipedia.org/wiki/Retina#mediaviewer/File:Fundus_photograph_of_normal_left_eye.jpg
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein
functions.

collagen

• A number of different forms

• All are rope-like proteins made of three polypeptides
wound together.
• About a quarter of all protein in the human body is
collagen
• Forms a mesh of fibres in skin and in blood vessel
walls that resists tearing.
• Gives strength to tendons, ligaments, skin and blood
vessel walls.
• Forms part of teeth and bones, helps to prevent
cracks and fractures to bones and teeth

https://en.wikipedia.org/wiki/Tooth_(human)#mediaviewer/File:Teeth_by_David_Shankbone.jpg
http://chempolymerproject.wikispaces.com/file/view/collagen_%28alpha_chain%29.jpg/34235269/collagen_%28alpha_chain%29.jpg
2.4.A1 Rubisco, insulin, immunoglobulins, rhodopsin, collagen and spider silk as examples of the range of protein functions.

• Different types of silk with different functions

spider silk • Dragline silk is stronger than steel and tougher than
Kevlar
• When first made it contains regions where the
polypeptide forms parallel arrays (bottom)
• Some regions seem like a disordered tangle (middle)
• When the stretched the polypeptide gradually
extends, making the silk extensible and very resistant
to breaking.

https://en.wikipedia.org/wiki/Spider_silk#mediaviewer/File:Araneus_diadematus_underside_1.jpg
https://en.wikipedia.org/wiki/Spider_silk#mediaviewer/File:Structure_of_spider_silk_thread_Modified.svg