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Peptide
Peptides are naturally occurring biological molecules. They are short chains of amino acid monomers
linked by peptide (amide) bonds. The covalent chemical bonds are formed when the carboxyl group of
one amino acid reacts with the amino group of another. The shortest peptides are dipeptides,
consisting of 2 amino acids joined by a single peptide bond, followed by tripeptides, tetrapeptides,
etc. A polypeptide is a long, continuous, and unbranched peptide chain. Hence, peptides fall under
the broad chemical classes of biological oligomers and polymers, alongside nucleic acids,
oligosaccharides and polysaccharides, etc.
Peptides are distinguished from proteins on the basis of size, and as an arbitrary benchmark can be
understood to contain approximately 50 or fewer amino acids. [1] Proteins consist of one or more
polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and
cofactors, or to another protein or other macromolecule (DNA, RNA, etc.), or to complex
macromolecular assemblies. Finally, while aspects of the techniques that apply to peptides versus
polypeptides and proteins differ (i.e., in the specifics of electrophoresis, chromatography, etc.), the
size boundaries that distinguish peptides from polypeptides and proteins are not absolute: long
peptides such as amyloid beta have been referred to as proteins, and smaller proteins like insulin
have been considered peptides.
Amino acids that have been incorporated into peptides are termed "residues" due to the release of
either a hydrogen ion from the amine end or a hydroxyl ion from the carboxyl end, or both, as a water
molecule is released during formation of each amide bond. [2] All peptides except cyclic peptides have
an N-terminal and C-terminal residue at the end of the peptide

Peptide classes
Peptides are divided into several classes, depending on how they are produced:

Milk peptides
Two naturally occurring milk peptides are formed from the milk protein casein when digestive
enzymes break this down; they can also arise from the proteinases formed by lactobacilli during the
fermentation of milk.[3]

Ribosomal peptides
Ribosomal peptides are synthesized by translation of mRNA. They are often subjected to proteolysis
to generate the mature form. These function, typically in higher organisms, as hormones and
signaling molecules. Some organisms produce peptides as antibiotics, such as microcins.[4] Since they
are translated, the amino acid residues involved are restricted to those utilized by the ribosome.
However, these peptides frequently have posttranslational modifications... such as phosphorylation,
hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are
linear, although lariat structures have been observed.[5] More exotic manipulations do occur, such as
racemization of L-amino acids to D-amino acids in platypus venom.[6]

Nonribosomal peptides
Nonribosomal peptides are assembled by enzymes that are specific to each peptide, rather than by
the ribosome. The most common non-ribosomal peptide is glutathione, which is a component of the
antioxidant defenses of most aerobic organisms.[7] Other nonribosomal peptides are most common in
unicellular organisms, plants, and fungi and are synthesized by modular enzyme complexes called
nonribosomal peptide synthetases.[8]

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These complexes are often laid out in a similar fashion, and they can contain many different modules
to perform a diverse set of chemical manipulations on the developing product. [9] These peptides are
often cyclic and can have highly complex cyclic structures, although linear nonribosomal peptides are
also common. Since the system is closely related to the machinery for building fatty acids and
polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates
that the compound was synthesized in this fashion. [10]

Peptones
Peptones are derived from animal milk or meat digested by proteolysis.[11] In addition to containing
small peptides, the resulting spray-dried material [clarification needed] includes fats, metals, salts, vitamins
and many other biological compounds. Peptones are used in nutrient media for growing bacteria and
fungi.[12]

Peptide fragments
Peptide fragments refer to fragments of proteins that are used to identify or quantify the source
protein.[13] Often these are the products of enzymatic degradation performed in the laboratory on a
controlled sample, but can also be forensic or paleontological samples that have been degraded by
natural effects.[14][15]

Peptides in Molecular Biology


Peptides received prominence in molecular biology for several reasons. The first is that peptides allow
the creation of peptide antibodies in animals without the need of purifying the protein of interest.[16]
This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be
used to make antibodies in a rabbit or mouse against the protein.
Another reason is that peptides have become instrumental in mass spectrometry, allowing the
identification of proteins of interest based on peptide masses and sequence. In this case the peptides
are most often generated by in-gel digestion after electrophoretic separation of the proteins.
Peptides have recently been used in the study of protein structure and function. For example,
synthetic peptides can be used as probes to see where protein-peptide interactions occur- see the
page on Protein tags.
Inhibitory peptides are also used in clinical research to examine the effects of peptides on the
inhibition of cancer proteins and other diseases. [17] For example, one of the most promising application
is through peptides that target LHRH.[18] These particular peptides act as an agonist, meaning that
they bind to a cell in a way that regulates LHRH receptors. The process of inhibiting the cell receptors
suggests that peptides could be beneficial in treating prostate cancer. However, additional
investigations and experiments are required before the cancer-fighting attributes, exhibited by
peptides, can be considered definitive. [19]

Well-known peptide families


The peptide families in this section are ribosomal peptides, usually with hormonal activity. All of these
peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to
exiting the cell. They are released into the bloodstream where they perform their signaling functions.
1.
2.
3.
4.

Tachykinin peptides
Vasoactive intestinal peptides
Pancreatic polypeptide-related peptides
Opioid peptides

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5.
6.

Calcitonin peptides
Other peptides
B-type Natriuretic Peptide (BNP) - produced in myocardium & useful in medical diagnosis
Lactotripeptides - Lactotripeptides might reduce blood pressure,[20][21][22] although the
evidence is mixed.[23]

Amino Acids

Proteins (building block of life) represent the polymers of alpha-amino acids, which can exist in either
dextro (D) or levo (L) form, also known as stereoisomers. Dextro and levo refer to the absolute
confirmation of optically active components. Aside from glycine, all other amino acids can be
described as mirror images not able to be superimposed. Major part of them, which are found in
nature, appear to be of the L-type. That's why eukaryotic proteins turn out to be always composed of
levo amino acids, despite the fact that dextro ones can be found in bacterial cell walls and a number
of peptide antibiotics. Thus far, more than three hundred kinds of amino acids have been discovered
in nature. However, only 20 of them are usually found as compounds of human peptides and proteins.
Molecule of an amino acid contains carboxyl (COOH) and amino (NH2) functional groups, and each
molecule features a different side chain, also known as R group, which vary greatly in properties.
Alanine is one of the standard amino acids.

Advantages
Aside from playing an important role in protein and enzyme synthesis, amino acids are considered
very crucial for your good health, since they contribute considerably to the health of the human
nervous system, hormone production, and muscular structure. In addition, they are needed for vital
organs and cellular structure. If a person experiences low levels of the essential amino acids, this may
cause hormonal imbalances, lack of concentration, irritability, and even depression.

Properties
Amino acids are crystalline solids able to dissolve in water. Meanwhile, they only dissolve sparingly in
organic solvents, and the extent of their solubility depends on the size and nature of the side chain.
Amino acids feature very high melting points - up to 200-300C, and other properties vary for each
particular amino acid.

Classifications
Experts classify amino acids based on lots of different features. One of them is whether or not people
can acquire them through the diet. According to this factor, scientists recognize 3 types: the
nonessential, essential, and conditionally essential amino acids. However, the classification as
essential or nonessential doesn't actually reflect their importance, as all twenty of them are necessary
for human health. Those 8 called essential (or indispensable) can't be produced by the body and

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therefore should be supplied by food: Leucine, Isoleucine, Lysine, Threonine, Methionine,
Phenylalanine, Valine, and Tryptophan. One more amino acid, Histidine, can be considered semiessential, as the human body doesn't always need dietary sources of it.
Meanwhile, conditionally essential amino acids aren't usually required in the human diet, but are able
to become essential under some circumstances. Finally, nonessential ones are produced by the
human body either out of the essential ones or from normal proteins breakdown. These include
Asparagine, Alanine, Arginine, Aspartic acid, Cysteine, Glutamic acid, Glutamine, Praline, Glycine,
Tyrosine, and Serine.
One more classification depends on the side chain structure, and experts recognize 5 types in this
classification:
1. containing sulfur (Cysteine and Methionine)
2. neutral (Asparagine, Serine, Threonine, and Glutamine)
3. acidic (Glutamic acid and Aspartic acid) and basic (Arginine and Lysine)
4. alphatic (these include Leucine, Isoleucine, Glycine, Valine, and Alanine)
5. aromatic (these include Phenylalanine, Tryptophan, and Tyrosine)
Finally, there's another classification based on structure of the side chain that divides the list of
twenty into 4 groups, two of which are main groups and two are subgroups: non-polar, polar, acidic
and polar, basic and polar. For example, side chains having pure hydrocarbon alkyl or aromatic groups
are considered non-polar, and their list includes Phenylalanine, Glycine, Valine, Leucine, Alanine,
Isoleucine, Proline, Methionine, and Tryptophan. Meanwhile, if the side chain contains different polar
groups like amides, acids, and alcohols, they are classified as polar. Their list includes Tyrosine,
Serine, Asparagine, Threonine, Glutamine, and Cysteine. Further classification goes for acidic-polar
(includes Aspartic Acid and Glutamic Acid), if the side chain has a carboxylic acid, and basic-polar
(includes Lysine, Arginine, and Histidine), if the side chain contains an amino group.

You might already know that a carbon atom can form up to 4 covalent bonds. If one carbon bonds to
more than 2 other carbons, a branch forms. That's why Valine, Leucine, and Isoleucine are called
branched-chain amino acids - their side-chains have a branch. Meanwhile, the combination of these 3
amino acids represent around one-third of skeletal muscle in your body.

Protein structure
Protein structure is the biomolecular structure of a protein molecule. Proteins are polymers
specifically polypeptides formed from sequences of amino acids. Each unit of a protein is called
an amino acid residue because it is the residue of every amino acid that forms the protein by losing
a water molecule. By convention, a chain under 40 residues is often identified as a peptide, rather
than a protein.[1] To be able to perform their biological function, proteins fold into one or more

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specific spatial conformations, driven by a number of non-covalent interactions such as hydrogen
bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. To understand the
functions of proteins at a molecular level, it is often necessary to determine their three-dimensional
structure. This is the topic of the scientific field of structural biology, which employs techniques such
as X-ray crystallography, NMR spectroscopy, and dual polarisation interferometry to determine the
structure of proteins.
Protein structures range in size from tens to several thousand residues. [2] By physical size, proteins
are classified as nanoparticles, between 1100 nm. Very large aggregates can be formed from
protein subunits. For example, many thousands of actin molecules assemble into a microfilament.
A protein may undergo reversible structural changes in performing its biological function. The
alternative structures of the same protein are referred to as different conformations, and transitions
between them are called conformational changes.

Levels of protein structure


There are four distinct levels of protein structure.

Amino acid residues


Each -amino acid consists of a backbone part that is present in all the amino acid types, and a side
chain that is unique to each type of residue. An exception from this rule is proline. Because the
carbon atom is bound to four different groups it is chiral, however only one of the isomers occur in
biological proteins. Glycine however, is not chiral since its side chain is a hydrogen atom. A simple
mnemonic for correct L-form is "CORN": when the C atom is viewed with the H in front, the residues
read "CO-R-N" in a clockwise direction.

Primary structure
The primary structure of a protein refers to the linear sequence of amino acids in the polypeptide
chain. The primary structure is held together by covalent bonds such as peptide bonds, which are
made during the process of protein biosynthesis or translation. The two ends of the polypeptide
chain are referred to as the carboxyl terminus (C-terminus) and the amino terminus (N-terminus)
based on the nature of the free group on each extremity. Counting of residues always starts at the
N-terminal end (NH2-group), which is the end where the amino group is not involved in a peptide
bond. The primary structure of a protein is determined by the gene corresponding to the protein. A
specific sequence of nucleotides in DNA is transcribed into mRNA, which is read by the ribosome in a
process called translation. The sequence of amino acids was discovered by Frederick Sanger. The
sequence of a protein is unique to that protein, and defines the structure and function of the protein.
The sequence of a protein can be determined by methods such as Edman degradation or tandem
mass spectrometry. Often, however, it is read directly from the sequence of the gene using the
genetic code. We know that there are over 10,000 proteins in the human body which are composed
of different arrangements of 20 types of amino acid residues. It is strictly recommended to use the
words "amino acid residues" when discussing proteins because when a peptide bond is formed, a
water molecule is lost, so proteins are made up of amino acid residues. Post-translational
modification such as disulfide bond formation, phosphorylations and glycosylations are usually also
considered a part of the primary structure, and cannot be read from the gene. For example, insulin
is composed of 51 amino acids in 2 chains. One chain has 31 amino acids, and the other has 20
amino acids.

Secondary structure

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Secondary structure refers to highly regular local sub-structures. Two main types of secondary
structure, the alpha helix and the beta strand or beta sheets, were suggested in 1951 by Linus
Pauling and coworkers.[3] These secondary structures are defined by patterns of hydrogen bonds
between the main-chain peptide groups. They have a regular geometry, being constrained to
specific values of the dihedral angles and on the Ramachandran plot. Both the alpha helix and
the beta sheet represent a way of saturating all the hydrogen bond donors and acceptors in the
peptide backbone. Some parts of the protein are ordered but do not form any regular structures.
They should not be confused with random coil, an unfolded polypeptide chain lacking any fixed
three-dimensional structure. Several sequential secondary structures may form a "supersecondary
unit".[4]

Tertiary structure
Tertiary structure refers to the three-dimensional structure of monomeric and multimeric protein
molecules. The alpha-helixes and beta pleated-sheets are folded into a compact globular structure.
The folding is driven by the non-specific hydrophobic interactions, the burial of hydrophobic residues
from water, but the structure is stable only when the parts of a protein domain are locked into place
by specific tertiary interactions, such as salt bridges, hydrogen bonds, and the tight packing of side
chains and disulfide bonds. The disulfide bonds are extremely rare in cytosolic proteins, since the
cytosol (intracellular fluid) is generally a reducing environment.

Quaternary structure
Quaternary structure is the three-dimensional structure of a multi-subunit protein and how the
subunits fit together. In this context, the quaternary structure is stabilized by the same non-covalent
interactions and disulfide bonds as the tertiary structure. Complexes of two or more polypeptides
(i.e. multiple subunits) are called multimers. Specifically it would be called a dimer if it contains two
subunits, a trimer if it contains three subunits, a tetramer if it contains four subunits, and a
pentamer if it contains five subunits. The subunits are frequently related to one another by
symmetry operations, such as a 2-fold axis in a dimer. Multimers made up of identical subunits are
referred to with a prefix of "homo-" (e.g. a homotetramer) and those made up of different subunits
are referred to with a prefix of "hetero-", for example, a heterotetramer, such as the two alpha and
two beta chains of hemoglobin.

Domains, Fotifs, and Folds in Protein Structure


Proteins are frequently described as consisting of several structural units. These units include
domains, motifs, and folds. Despite the fact that there are about 100,000 different proteins
expressed in eukaryotic systems, there are many fewer different domains, structural motifs and
folds.

Structural domain
A structural domain is an element of the protein's overall structure that is self-stabilizing and often
folds independently of the rest of the protein chain. Many domains are not unique to the protein
products of one gene or one gene family but instead appear in a variety of proteins. Domains often
are named and singled out because they figure prominently in the biological function of the protein
they belong to; for example, the "calcium-binding domain of calmodulin". Because they are
independently stable, domains can be "swapped" by genetic engineering between one protein and
another to make chimera proteins.

Structural and sequence motif


The structural and sequence motifs refer to short segments of protein three-dimensional structure or
amino acid sequence that were found in a large number of different proteins.

Supersecondary structure
The supersecondary structure refers to a specific combination of secondary structure elements, such
as beta-alpha-beta units or a helix-turn-helix motif. Some of them may be also referred to as
structural motifs.

Protein fold
A protein fold refers to the general protein architecture, like a helix bundle, beta-barrel, Rossman
fold or different "folds" provided in the Structural Classification of Proteins database.[5]

Superdomain
A superdomain consists of two or more nominally unrelated structural domains that are inherited as
a single unit and occur in different proteins. [6] An example is provided by the protein tyrosine
phosphatase domain and C2 domain pair in PTEN, several tensin proteins, auxilin and proteins in
plants and fungi. The PTP-C2 superdomain evidently came into existence prior to the divergence of
fungi, plants and animals is therefore likely to be about 1.5 billion years old.

Protein folding
Once translated by a ribosome, each polypeptide folds into its characteristic three-dimensional
structure from a random coil.[7] Since the fold is maintained by a network of interactions between
amino acids in the polypeptide, the native state of the protein chain is determined by the amino acid
sequence (Anfinsen's dogma).[8]

Protein Structure Determination


Around 90% of the protein structures available in the Protein Data Bank have been determined by Xray crystallography. This method allows one to measure the three-dimensional (3-D) density
distribution of electrons in the protein, in the crystallized state, and thereby infer the 3-D
coordinates of all the atoms to be determined to a certain resolution. Roughly 9% of the known
protein structures have been obtained by nuclear magnetic resonance techniques. The secondary
structure composition can be determined via circular dichroism. Vibrational spectroscopy can also
be used to characterize the conformation of peptides, polypeptides, and proteins. [9] Cryo-electron
microscopy has recently become a means of determining protein structures to high resolution, less
than 5 angstroms or 0.5 nanometer, and is anticipated to increase in power as a tool for high
resolution work in the next decade. This technique is still a valuable resource for researchers
working with very large protein complexes such as virus coat proteins and amyloid fibers. A more
qualitative picture of protein structure is often obtained by proteolysis, which is also useful to screen
for more crystallizable protein samples. Novel implementations of this approach, including fast
parallel proteolysis (FASTpp), can probe the structured fraction and its stability without the need for
purification.[10]

Structure Classification
Protein structures can be grouped based on their similarity or a common evolutionary origin. The
Structural Classification of Proteins database[11] and CATH database[12] provide two different
structural classifications of proteins. Shared structure between proteins is considered evidence of
evolutionary relatedness between proteins and is used group proteins together into protein
superfamilies.

Computational Prediction of Protein Structure

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The generation of a protein sequence is much easier than the determination of a protein structure.
However, the structure of a protein gives much more insight in the function of the protein than its
sequence. Therefore, a number of methods for the computational prediction of protein structure
from its sequence have been developed.[14] Ab initio prediction methods use just the sequence of the
protein. Threading and homology modeling methods can build a 3-D model for a protein of unknown
structure from experimental structures of evolutionarily-related proteins, called a protein family.

Protein Structure
Proteins are chains of amino acids that fold into a three-dimensional shape. Proteins come in a wide
variety of amino acid sequences, sizes, and three-dimensional structures, which reflect their diverse
roles in nearly all cellular functions. Each protein has a particular structure necessary to bind with a
high degree of specificity to one or a few molecules and to carry out its function; thus, function is
directly correlated to structure of the protein. Proteins make up about 50 percent of the dry weight
of cells and are the most abundant of the macromolecules inside the cell and of the cellular
membranes. Proteins (including their lipoprotein and glycoprotein forms) also constitute 10 percent
of the weight of the blood plasma of living organisms, carrying various nutrients throughout the
body and acting as signals to coordinate bodily functions between the different organs.
The sizes of proteins vary greatly. The size is described by the molecular weight given in the units of
a dalton. One dalton is the molecular mass of one hydrogen atom. The molecular weight of a protein
is equal to the addition of the molecular weights of the amino acids constituting the protein. Some
proteins are of relatively small molecular size, such as insulin, with a molecular weight of about
5,700 daltons. Others, like titin (a protein found in muscle), are very large. Some proteins consist of
a single amino acid sequence (polypeptide chain), while others are multimers of the same or
different subunits.

Organization of Protein Structure


There are four levels of protein structure: primary, secondary, tertiary, and quaternary. These levels
also reflect their temporal sequence. Proteins are synthesized as a primary sequence and then fold
into secondary tertiary and quaternary structures. The figures show these various types of
structure, which are described as follows.
Amino acids are the building blocks (units) of proteins. Each amino acid has several common
features: an amino and a carboxyl chemical group both bonded to the alpha carbon (C) and an R
group that defines a particular amino acid. Some R groups are hydrophobic and tend to project to,
and be buried in, the inside of a protein structure. Four amino acid R groups contain either a positive
or negative charge and thus project to the water environment to the exterior of proteins. Other R
groups are polar in nature and also tend to project to the outside.
The amino acids of a protein are connected to each other by peptide bonds . During protein
synthesis the amino group of the amino acid being added is coupled to the carboxyl group of the
prior amino acid, and two hydrogen atoms and one oxygen atom are removed as a water molecule
(H 2 O) and the peptide bond is formed .

Primary Structure of Proteins


The linear sequence of amino acids constitutes a protein's primary structure. The sequence is
written from the amino-terminal end (the first amino acid) to the carboxyl-terminal end (the same
sequence in which the protein is synthesized). All properties of a protein are derived from the
primary structure, the linear sequence. Encoded in the sequence is the ability of the protein to fold
into its secondary, tertiary, and quaternary structures, and thus to be able to carry out a function.
The function of a protein is only expressed when the protein has achieved its three-dimensional
shape.

Secondary Structures of Proteins


Secondary structures arise from non-covalent interactions between amino acids across the chain.
There are only two bonds that can rotate in space between each amino acid in the backbone of the
primary sequence. These restricted movements, when repeated through several amino acids in a
chain, yield the two main types of protein secondary structure: the alpha () helix and the beta ()
strand.
The helix is shaped like a spiral staircase, with each step representing a single amino acid. Each
3.6 amino acids complete a 360-degree turn in the helix. If a helical portion of a protein contained
36 amino acids, there would be 10 complete turns in the helix. Each amino acid projects an R group
to the outside of the staircase. helices of proteins vary in length from 5 to 40 amino acids with an
average of about 10. Certain proteins are made up entirely of helices (and the loops connecting the
helices) such as the subunits of hemoglobin , which contain 8 helices.
As the name "strand" implies, the amino acids of the strand form a linear structure. However, the
bond angles along the peptide backbone produce a regular zigzag pattern within this linear
structure. Adjacent R groups project in opposite directions. When amino acid sequences fold into a
three-dimensional structure of strands, one amino acid R group will then project to the interior of the
protein and the adjacent R group will project to the outside (to the water environment).
strands of proteins may be arranged adjacent to each other like strings on an instrument to form
what is termed a sheet. The strands of a sheet may be parallel in orientation (all the
sequences running from amino- to carboxyl-terminal) or antiparallel (that is, the strands alternate in
orientation).
To form a complete protein, the helices or strands must be joined together through the amino acid
sequence. The amino acids that make up these joining regions are called "loops." For example, two
adjacent antiparallel strands of a sheet are often connected by a loop consisting of two or three
amino acids. Loops also connect segments of helices and connect strands that are adjacent to
helices in a protein sequence. Some loop regions can be very long, consisting of up to twenty-one
amino acids; but, most commonly, they are between two and ten amino acids.

Tertiary Structures of Proteins


The three-dimensonal structure of a single polypeptide chain is termed its tertiary structure.
Tertiary structures are different combinations of the secondary structures ( helices, strands, and
loops). Tertiary structure is subdivided into certain portions that are termed motifs and domains.
Motifs are simple combinations of secondary structure that occur in many different proteins and
which carry out a similar function. An example is the helix-loop helix. It consists of two antiparallel
helices at about a 60-degree angle to each other connected by a loop. This motif, which binds the
calcium ion , is found in several proteins that regulate cellular activity via changes in calcium ion
concentrations. Many proteins that bind to deoxyribonucleic acid (DNA) and regulate gene
expression incorporate a zinc finger motif. As the name implies, this motif binds the zinc ion using
combinations of the amino acids cysteine and histidine. One type of zinc finger motif consists of a
single helix opposite two strands in an antiparallel arrangement. The zinc ion is held between
the helix and the two strands using two histidine R groups from the helix and two cysteine R
groups.

Levels of protein structure


Alpha helices and beta sheets are linked by less-structured loop regions to form domains, which
combine to form larger subunits and ultimately functional proteins from the strands. Another motif
common to DNA binding proteins is the leucine zipper, in which two parallel helices are adjacent

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to each other with the leucine side chains projecting from each helix binding together and thus
binding the two helices together.
A single polypeptide chain may fold into one or more domains to yield the tertiary structure of a
protein. The eight helices of a subunit of hemoglobin connected by seven loop regions constitute
the globin domain. Two sheets (each of four antiparallel strands) form a " barrel" structure
domain that is repeated in the immunoglobulin proteins. Each domain can express a distinct
function and is sometimes arranged in a single protein to efficiently carry out an overall function
that has several parts. For example, there are seven different chemical reactions that act in
sequence to synthesize a fatty acid. In mammals, the fatty acid synthetase enzyme is a single
polypeptide chain folded into seven domains, each domain carrying out one of the seven chemical
reactions.

Quaternary Structures of Proteins


Two or more polypeptide chains may bind to each other to form a quaternary structure. The
quaternary structure of hemoglobin, for example, consists of four polypeptide chains, two , and
two subunits arranged in space in a defined manner.

How Does Protein Structure Determine Function?


For almost all biological functions to be expressed, two molecules must bind to each other. An
antibody protein must bind to an antigen to provoke an immune response, a hormone protein (for
example, a growth factor) must bind to a cell surface receptor to trigger a cell reaction, an enzyme
protein must bind to a substrate to catalyze a reaction, and a protein containing the leucine zipper
motif must bind to DNA to regulate gene expression. In order for two molecules to bind, they must
recognize each other and form a series of noncovalent bonds. Recognition of two molecules for each
other is termed "structural complementarity"; that is, the three-dimensional structures must
complement each other in the shapes of the interacting surfaces. Analogies that have been used are
a key fitting into a lock or the wooden square of a simple child's game that fits into the squareshaped cutout of a puzzle board.
"Ligand" is the general term used to denote the molecule bound by the protein. When a protein
binds to a ligand, many noncovalent bonds are formed. These may be ionic bonds between the
charged acidic or basic groups of side chains of amino acids, or hydrogen bonds whereby a
hydrogen proton is shared between two atoms, or a weak force of binding termed van der Waals
bonding that can occur between any two atoms that are very close in space. Water may also be
excluded from the surfaces of two molecules binding to each other, contributing what is called the
hydrophobic effect. The number of such noncovalent bonds formed between two molecules directly
relates to the strength (the affinity ) of binding. Thus strength of binding can be strong, as in the
case of a protein hormone binding to a cell surface receptor, or weak, as with binding to their
substrate enzymes.
Binding of ligands occurs on certain portions of the protein surface. All three types of secondary
structure (or combinations of secondary structure) can be involved in binding a particular ligand.
The immunoglobulin molecule uses a total of six loop structures, three each from the variable
domains of the heavy and light chains to bind to an antigen. By a very large number of variations of
the spatial relationships of these loop regions and differences in amino acid residues of the loops,
immunoglobulins exhibit binding activities to a very large number of antigens that are encountered
in the environment.
For instance, DNA-binding proteins often use helices to recognize and bind to the nucleic acids of
DNA sequences. Different sequences of amino acids along the helices allow such gene regulatory
proteins to recognize specific nucleic acid sequences of the DNA and thus to alter expression of a
single or only a few genes. The hexokinase protein binds both glucose and ATP to form glucosephosphate, the first step in the metabolism of glucose through the glycolytic pathway. The

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hexokinase protein has two domains, and the glucose spatially complements within a groove
between the two domains and thus is bound by the enzyme. Galactose is another sugar very similar
to glucose except for the spatial orientation of one of five hydroxyl groups common to glucose and
galactose. This single hydroxyl orientation difference does not allow galactose to bind to hexokinase
and thus hexokinase exhibits specificity of binding. Galactose is phosphorylated by another enzyme
protein, galactokinase, which exhibits specificity for the galactose sugar; that is, galactokinase
structurally complements and binds galactose, but not glucose.

Protein Modifications
Proteins can be glycosylated (glycoproteins) or associated with lipids (lipoproteins).

Glycoprotein
Glycoproteins have attached carbohydrate molecules (residues). Carbohydrate residues are added
to the protein structure and modified during and following protein synthesis. There are many
different carbohydrate sequences found in glycoproteins, many of which have functional
consequences. In general, most proteins that are secreted from cells are glycosylated. Most of the
proteins in serum are glycosylated as are the proteins found in saliva and the digestive juices of the
gastrointestinal tract. Carbohydrates have many hydroxyl (-OH) groups that bind to water
molecules, and thus increase stability. Thus the glycoproteins of saliva tend to lubricate the food
chewed, in part to allow easier swallowing of food and its passage through the esophagus . The
glycoproteins secreted in the stomach protect the lining of that organ from its acidic environment.
This protective role of carbohydrates is also apparent for the serum glycoproteins. The
carbohydrates on the surface of the protein protect the protein from the actions of proteases that
degrade protein structures.
Certain types of carbohydrate residues on glycoproteins also serve as signal mechanisms. If a tissue
is injured or becomes infected, certain glycoproteins are recruited to the surfaces of endothelial cells
(the cells that line all blood vessels), where they are recognized by white blood cells, as a signal that
this is a site of injury requiring attention. Particularly in the last ten years, about three hundred
functions of the carbohydrate portions of glycoproteins have been described.

Lipoproteins
Lipoproteins are complexes between a particular set of proteins (termed apoproteins) and lipids
(phospholipids, triglycerides, cholesterol, and cholesterol esters). These lipids are transported
throughout the body as the complex lipoproteins. Humans have nine different apoproteins of various
molecular sizes and concentrations in the blood. Portions of the surfaces of apoproteins exhibit
specificity and bind the various lipids, providing the scaffold upon which the lipoprotein particles are
constructed. Their densitieshigh-density (HDL), low-density (LDL), and very-lowdensity lipoproteins
(VLDL)are used to characterize the protein. The apoproteins are synthesized in the cell (mainly in
the liver) and acquire lipids to become HDL, LDL, or VLDL.

Proteins and Evolution


The presence of similar domain structures in different proteins, the duplication of domain structures
in a single protein, and similarities in amino acid sequences (sequence homologies) indicate an
evolutionary relationship of many proteins in a single species and between species. There are many
examples of these relationships, of which a few will be described here.
The globin fold, as described above, consists of eight helices (connected by loops) that form a
pocket as an active site . A heme structure is bound in many globin fold proteins that binds and
carries oxygen in an organism. The globin fold structure has been preserved in mammals, insects,
and plants although the amino acid sequence similarities may be very low between such disparate

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species. Thus, natural selection has maintained similar structures to carry out similar functions even
as the gene sequences have diverged to such a great extent between the different species.
The helix-turn-helix motif is common to many gene repressor proteins that bind to DNA sequences.
Rigorous statistical analyses of the amino acid sequences of these motifs suggest that these
repressor proteins all evolved from a common ancestral gene and that certain amino acid residues
in the motif structure are crucial to maintain the helix-turn-helix structure of the motif.
Serine proteases (for example, chymotrypsin, a digestive enzyme in mammals) consist of two
barrel domains, the ends of which come together to form an active site. Within the active site is a
catalytic triad, which consists of three amino acids (histidine, serine, and cysteine) arranged in
space to catalyze the hydrolysis of a peptide bond. The two barrels probably evolved from
duplication of a common gene. In humans, there are many serine proteases that cleave peptide
bonds of different proteins. All have the same two barrel domain structure with the same spatial
catalytic triad. Specificity of binding and cleaving different proteins is achieved by altering the
sequences around the catalytic triad such that different proteins complement the different binding
sites.

Protein Structures and Disease


Some differences of amino acid sequences of proteins are directly related to disease. A well-defined
example is that of sickle-cell disease. A single difference at position number 6 in the amino acid
sequence of the chain of hemoglobin (a valine amino acid is found in the person with sickle-cell
disease instead of glutamic acid) results in aggregation of the hemoglobin molecules with
consequent elongation (the sickle shape) and fragility of the red blood cells. The disease cystic
fibrosis has now been defined as mutations in a particular gene that codes for a cell membrane
protein that functions to pump chloride ions out of the cell. This protein in cystic fibrosis is defective
in this function because the amino acid sequence is different from normal.

Role of Proteins in Living Organisms


Rightly regarded as one of the building blocks of life, proteins do much more than just nourish our
body. Here, we have tried to provide you an insight on their significance in living beings.
You probably know protein is an essential macro-nutrient and vital for good health. You incorporate
various sources of proteins like eggs, milk, fish, beans, lentils, and nuts in your daily diet. But what
exactly do proteins do for you? Why do you need them? Let's find out the answers.

Structure
It is important to understand that the structure or makeup of protein molecules determines its
functions. Proteins are essentially macromolecules that are made of polypeptide chains. A protein
molecule can be formed of a single polypeptide chain or more. Each polypeptide chain comprises a
long and continuous string of amino acids that are held together by peptide bonds. These bonds are
formed between the carboxyl (-COOH) group of one amino acid and the amino (-NH2- group) of the
adjacent amino acid. The type and number of these amino acids arranged in a linear fashion give
rise to the varied types of proteins found in nature. Proteins are synthesized in the cell cytoplasm
through a process called translation. In this process the mRNA, produced in the cell nucleus
(transcription), is transported to the cytoplasm via the nuclear membrane. Here, the ribosomes
utilize the mRNA as a template and produce proteins.

Role of Proteins
Once digested, proteins break down into their constituent amino acids, which is classified into
essential or non-essential. Essential amino acids cannot be synthesized by our body, hence they

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have to be supplemented by food sources. Non essential ones can be synthesized by our body. They
have the following functions:

Energy source: Proteins are a source of energy like carbohydrates and fats. Equal weights of

carbohydrates and proteins provide the same amount of energy (in calories). When we eat proteinrich food, they are broken down into constituent amino acids by enzymes.
Our bodies are incapable of storing proteins in the same form. An extra intake will result in
converting the proteins into fat (for storage) or energy (for consumption).
These are then used by living cells as fuel for building new muscles, cartilages, and repairing any
damaged tissue or
cell. There are various plant sources (pulses, beans, soya, etc) and animal sources (meat, fish,
poultry) of protein that are a part of our diet. Casein supplies the body with the nutrition required to
develop bones and encasing muscle. In plant systems they play a vital role in germination. The
stored proteins act as a source of nitrogen for the growing embryo, supplying it with necessary
energy.

Structural Support to Living Cells: One of the most important functions of proteins is to

provide structural identity to living organisms. Fibrous proteins, called collagen, provide strength,
firmness, and structure to body cells and tissues, holding them together in place. Without their
presence, cells would not be able to hold together, and tissues and organs would collapse.
Connective tissues like adipose tissue, cartilage, tendons, and ligaments are composed of this
protein. Keratin forms the protective barrier for most living beings. It makes up the outermost layer
of our skin, nails, and hair. In animals, it helps in developing horns, fur, and scales, while in birds it
develops beaks, feathers, and claws.

Transporters: According to the fluid mosaic model our cell membranes are composed of proteins

and lipids. Globular proteins and transmembrane proteins help in regulating the flow of small ions
and molecules like sodium ions and glucose molecules through the cells. The transport of such
molecules occurs through the process of diffusion. Transmembrane proteins extend on either side of
the cell membrane that act as a regulator by allowing or denying the entry of ions and molecules.
Globular proteins act as carriers by binding to molecules and facilitating its transportation into the
cell membrane. Once transported, these proteins detach themselves from the molecules. Transferrin
is an example of a transport protein. It carries iron within the immune system.

Biochemical catalysts: Enzymes are proteinaceous in nature. They help in catalyzing

(increasing the rate of a reaction) various important biochemical processes like glycolysis. They do
so by lowering the minimum energy required to carry out a biochemical process, called activation
energy. Each enzyme binds to only a specific substrate and increases the rate of conversion of the
substrate into other products. These products are then readily used by living bodies to maintain
normal growth and development. For example, enzyme Hexokinase acts on glucose (substrate) to
give a series of products that are acted upon by various enzyme-releasing ATP molecules (energy)
for cell metabolism.

Hormones: Hormones are proteins that function as chemical messengers. When secreted they act
on their target cells, tissues, and organs. They bind to a specific receptor present on the surface of
the target. Once attached, they lead to a cascade of signaling responses. These responses are
essential for an individual's physical and mental wellness. Plants also have hormones, called
phytohormones. An example of human hormones is growth hormones. As the name suggests, it
helps in the overall growth of a living body. Another example is insulin which is a hormone secreted
by the pancreas. This is released in the blood and regulates its sugar levels.

Soldiers of Immune System: The immune system helps in defending the body against diseasecausing microbes, contaminants, and other foreign bodies. Most immune responses are carried out
by protein entities. For example, antibodies are produced by B cells of the immune system that are
highly specific for a particular antigen (foreign bodies like bacteria etc.). These antibodies help in

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eradicating and neutralizing the harmful pathogens. Also, the complement system of our immune
system has a number of small protein molecules. These proteins like C3, C9, etc., get activated in a
stepwise fashion creating pores on the cell membranes of the target (bacteria, viruses, etc). This
leads the membrane to rupture and ultimately cell lysis. In case of an injury, fibrinogen, a protein in
the blood plasma, forms fibrin. Fibrin, literally, seals off the wound and does not permit the entry of
any foreign infection.

Buffering Action: We know that blood acts as a medium of transportation in human and animal

bodies. It supplies vital nutrients, hormones, antibodies, etc., to various organs of the body.
However, it maintains a steady pH environment for carrying out its functions properly. This pH is
maintained by the protein buffering system along with bicarbonate and phosphate buffering system.
The proteins have amino groups and carboxyl groups making them capable of donating and
accepting hydrogen ions. Hence, when our blood becomes too acidic or basic, they accept or donate
H+ ions. This ensures a neutral pH of 7.4 in the blood.
We have tried to summarize the significance of proteins in brief, however, there are millions of
proteins in our living system. They work in tandem with other biomolecules to sustain life. Hence, a
person should have appropriate intake of proteins in his diet. This will ensure proper growth and
development, both mentally and physically. It is important to understand that deficiency of proteins
can lead to various diseases like kwashiorkor, marasmus, cachexia, etc. These have high mortality
rate and should be dealt with immediately. The amino acids are vital for the replacement of what the
human anatomy is not capable of doing itself.
Did You Know?
In case of protein deficiency, our body draws amino acids from muscles and other protein-rich cells
and tissues for survival!

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