Protein its shape ,structure and functions

Protein Structure and Function

Protein
• Proteins are the building blocks from which cells are assembled, and they constitute
most of the cell’s dry mass. But in addition to providing the cell with shape and
structure, proteins also execute nearly all its myriad functions.
• Enzymes promote intracellular chemical reactions by providing intricate molecular
surfaces, contoured with particular bumps and crevices, that can cradle or exclude
specific molecules.
• Other proteins carry messages from one cell to another, or act as signal integrators
that relay information from the plasma membrane to the nucleus of individual cells.
• Yet others serve as tiny molecular machines with moving parts: some proteins, such
as kinesin, propel organelles through the cytoplasm; others, such as helicases, open
double-stranded DNA molecules.
• Specialized proteins also act as antibodies, toxins, hormones, antifreeze molecules,
elastic fibers, or luminescence generators.

The Shape and Structure of proteins
• A protein molecule is made from a long chain of 20 amino acids, each linked to its
neighbor through a covalent peptide bond (figure 4–1). Proteins are therefore referred to
as polypeptides or polypeptide chains.
• In each type of protein, the amino acids are present in a unique order, called the amino
acid sequence, which is exactly the same from one molecule of that protein to the next.
• Each polypeptide chain consists of a backbone that supports the different amino acid side
chains.
• The polypeptide backbone is made from the repeating sequence of the core atoms of the
amino acids that form the chain.
• Projecting from this repetitive backbone are any of the 20 different amino acid side chains
—the parts of the amino acids that are not involved in forming the peptide bond (figure
4–2).
• These side chains give each amino acid its unique properties. Some are nonpolar
and hydrophobic (“water-fearing”), some are negatively or positively charged,
some are chemically reactive, and so on.

• Long polypeptide chains are very flexible: many of the covalent bonds
that link carbon atoms in an extended chain of amino acids allow free
rotation of the atoms they join.
• Thus proteins can in principle fold in an enormous number of ways.
Each folded chain is constrained by many different sets of weak
noncovalent bonds that form within proteins. These bonds involve atoms
in the polypeptide backbone as well as atoms in the amino acid side
chains.
• The noncovalent bonds that help proteins maintain their shape include
hydrogen bonds, electrostatic attractions, and van der Waals attractions.
Because individual noncovalent bonds are much weaker than covalent
bonds, it takes many noncovalent bonds to hold two regions of a
polypeptide chain together tightly.
• The stability of each folded shape will therefore be affected by the
combined strength of large numbers of noncovalent bonds (figure 4–4).

• A fourth weak force, hydrophobic interaction, also plays a central role in determining
the shape of a protein. In an aqueous environment, hydrophobic molecules, including
the nonpolar side chains of particular amino acids, tend to be forced together to
minimize their disruptive effect on the hydrogen-bonded network of the surrounding
water molecules.
• Therefore, an important factor governing the folding of any protein is the
distribution of its polar and nonpolar amino acids.
• The nonpolar (hydrophobic) side chains—which belong to amino acids such as
phenylalanine, leucine, valine, and tryptophan—tend to cluster in the interior of the
folded protein and can avoid contact with the aqueous cytosol that surrounds them inside
a cell.
• In contrast, polar side chains—such as those belonging to arginine, glutamine, and
histidine—tend to arrange themselves near the outside of the folded protein, where they
can form hydrogen bonds with water and with other polar molecules (figure 4–5).
• When polar amino acids are buried within the protein, they are usually hydrogen-bonded
to other polar amino acids or to the polypeptide backbone (figure 4–6).

The Primary Structure of a Protein Is
Its Linear Arrangement of Amino Acids
• The repeated amide N, carbon (C), and carbonyl C atoms of each amino acid
residue form the backbone of a protein molecule from which the various side-
chain groups project (Figure 3-2).
• As a consequence of the peptide linkage, the backbone exhibits directionality
because all the amino groups are located on the same side of the C atoms. Thus
one end of a protein has a free (unlinked) amino group (the N-terminus) and the
other end has a free carboxyl group (the C-terminus). The sequence of a protein
chain is conventionally written with its N-terminal amino acid on the left and its
C-terminal amino acid on the right.

• The primary structure of a protein is simply the linear arrangement,
or sequence, of the amino acid residues that compose it. Many terms
are used to denote the chains formed by the polymerization of amino
acids. A short chain of amino acids linked by peptide bonds and
having a defined sequence is called a peptide; longer chains are
referred to as polypeptides.
• Peptides generally contain fewer than 20–30 amino acid residues,
whereas polypeptides contain as many as 4000 residues. We generally
reserve the term protein for a polypeptide (or for a complex of
polypeptides) that has a well-defined three-dimensional structure. It is
implied that proteins and peptides are the natural products of a cell.

Secondary Structure of Protein
The Alpha helix and the Beta Sheet are common folding patterns
• When the three-dimensional structures of many different protein molecules are compared,
it becomes clear that, although the overall conformation of each protein is unique, two
regular folding patterns are often present. Both were discovered more than 50 years ago
from studies of hair and silk.
• The first folding pattern to be discovered, called the α helix, was found in the protein α -
keratin, which is abundant in skin and its derivatives—such as hair, nails, and horns.
• Within a year of the discovery of the α helix, a second folded structure, called a β sheet,
was found in the protein fibroin, the major constituent of silk.
• These two folding patterns are particularly common because they result from hydrogen
bonds that form between the N–H and C=O groups in the polypeptide backbone.
Because the amino acid side chains are not involved in forming these hydrogen bonds, a
helices and b sheets can be generated by many different amino acid sequences. In each
case, the protein chain adopts a regular, repeating form or motif.

The α Helix
• In a polypeptide segment folded into an α helix, the carbonyl oxygen atom of
each peptide bond is hydrogen bonded to the amide hydrogen atom of the
amino acid four residues toward the C-terminus.
• This periodic arrangement of bonds confers a directionality on the helix
because all the hydrogen-bond donors have the same orientation (Figure 3-3).
• The stable arrangement of amino acids in the helix holds the backbone in a
rodlike cylinder from which the side chains point outward.
• The hydrophobic or hydrophilic quality of the helix is determined entirely
by the side chains because the polar groups of the peptide backbone are
already engaged in hydrogen bonding in the helix.

The β Sheet
• Another type of secondary structure, the β sheet, consists of laterally packed
strands. Each strand is a short (5- to 8-residue), nearly fully extended polypeptide
segment.
• Hydrogen bonding between backbone atoms in adjacent strands, within either the
same polypeptide chain or between different polypeptide chains, forms a sheet
(Figure 3-4a).
• The planarity of the peptide bond forces a sheet to be pleated; hence this structure
is also called a pleated sheet, or simply a pleated sheet.
• Like helices, strands have a directionality defined by the orientation of the
peptide bond. Therefore, in a pleated sheet, adjacent strands can be oriented in the
same (parallel) or opposite (antiparallel) directions with respect to each other.
• In both arrangements, the side chains project from both faces of the sheet (Figure
3-4b). In some proteins, sheets form the floor of a binding pocket; the
hydrophobic core of other proteins contains multiple sheets.

Tertiary Structure
• Tertiary structure refers to the overall conformation of a polypeptide chain—that is, the
three-dimensional arrangement of all its amino acid residues.
• In contrast with secondary structures, which are stabilized by hydrogen bonds, tertiary
structure is primarily stabilized by hydrophobic interactions between the nonpolar
side chains, hydrogen bonds between polar side chains, and peptide bonds.
• Because the stabilizing interactions are weak, however, the tertiary structure of a protein
is not rigidly fixed but undergoes continual and minute fluctuation. This variation in
structure has important consequences in the function and regulation of proteins.

Structural and Functional Domains
Are Modules of Tertiary Structure
• The tertiary structure of proteins larger than 15,000 MW is typically subdivided into
distinct regions called domains.
• Structurally, a domain is a compactly folded region of polypeptide. For large proteins,
domains can be recognized in structures determined by x-ray crystallography or in images
captured by electron microscopy.
• Although these discrete regions are well distinguished or physically separated from
one another, they are connected by intervening segments of the polypeptide chain.
• Each of the subunits in hemagglutinin, for example, contains a globular domain and a
fibrous domain (Figure 3-7a).
• A structural domain consists of 100–150 residues in various combinations of motifs.
Often a domain is characterized by some interesting structural feature: an unusual
abundance of a particular amino acid (e.g., a proline-rich domain, an acidic domain),
sequences common to (conserved in) many proteins (e.g., SH3, or Src homology region
3), or a particular secondary-structure motif (e.g., zinc-finger motif in the kringle
domain).

• Domains are sometimes defined in functional terms on the basis of observations that an
activity of a protein is localized to a small region along its length.
• For instance, a particular region or regions of a protein may be responsible for its catalytic
activity (e.g., a kinase domain) or binding ability (e.g., a DNA-binding domain, a membrane-
binding domain).
• Functional domains are often identified experimentally by whittling down a protein to its
smallest active fragment with the aid of proteases, enzymes that cleave the polypeptide
backbone.
• Alternatively, the DNA encoding a protein can be subjected to mutagenesis so that segments
of the protein’s backbone are removed or changed.
• The activity of the truncated or altered protein product synthesized from the mutated gene is
then monitored and serves as a source of insight about which part of a protein is critical to its
function.

Proteins Associate into Multimeric Structures and
Macromolecular Assemblies
• Multimeric proteins consist of two or more polypeptides or subunits. A fourth
level of structural organization, quaternary structure, describes the number
(stoichiometry) and relative positions of the subunits in multimeric proteins.
• Hemagglutinin, for example, is a trimer of three identical subunits held together
by noncovalent bonds (Figure 3-7b). The multimeric nature of many proteins is
critical to mechanisms for regulating their function.
• In addition, enzymes in the same pathway may be associated as subunits of a large
multimeric protein within the cell, thereby increasing the efficiency of pathway
operation.
• The highest level of protein structure is the association of proteins into
macromolecular assemblies. Typically, such structures are very large, exceeding 1
mDa in mass, approaching 30–300 nm in size, and containing tens to hundreds of
polypeptide chains, as well as nucleic acids in some cases.

• Macromolecular assemblies with a structural function include the capsid that
encases the viral genome and bundles of cytoskeletal filaments that support and
give shape to the plasma membrane.
• Other macromolecular assemblies act as molecular machines, carrying out the
most complex cellular processes by integrating individual functions into one
coordinated process. For example, the transcriptional machine that initiates the
synthesis of messenger RNA (mRNA) consists of RNA polymerase, itself a
multimeric protein, and at least 50 additional components including general
transcription factors, promoter-binding proteins, helicase, and other protein
complexes

Many Proteins Undergo Chemical Modification of Amino Acid
Residues
• Nearly every protein in a cell is chemically modified after its synthesis on a ribosome.
Such modifications, which may alter the activity, life span, or cellular location of proteins,
entail the linkage of a chemical group to the free –NH2 or –COOH group at either end of
a protein or to a reactive sidechain group in an internal residue.
• Although cells use the 20 amino acids to synthesize proteins, analysis of cellular proteins
reveals that they contain upward of 100 different amino acids. Chemical modifications
after synthesis account for this difference.
• Acetylation, the addition of an acetyl group (CH3CO) to the amino group of the N-
terminal residue, is the most common form of chemical modification, affecting an
estimated 80 percent of all proteins.

• This modification may play an important role in controlling the life
span of proteins within cells because nonacetylated proteins are
rapidly degraded by intracellular proteases.
• Residues at or near the termini of some membrane proteins are
chemically modified by the addition of long lipidlike groups.
• The attachment of these hydrophobic “tails,” which function to anchor
proteins to the lipid bilayer, constitutes one way that cells localize
certain proteins to membranes.

Peptide Segments of Some Proteins Are Removed After
Synthesis
• After their synthesis, some proteins undergo irreversible changes that do not entail changes in
individual amino acid residues. This type of post-translational alteration is sometimes called
processing.
• The most common form is enzymatic cleavage of a backbone peptide bond by proteases, resulting in
the removal of residues from the C- or N-terminus of a polypeptide chain. Proteolytic cleavage is a
common mechanism for activating enzymes that function in blood coagulation, digestion, and
programmed cell death.
• Proteolysis also generates active peptide hormones, such as EGF and insulin, from larger precursor
polypeptides.
• An unusual and rare type of processing, termed protein self-splicing, takes place in bacteria and
some eukaryotes. This process is analogous to editing film: an internal segment of a polypeptide is
removed and the ends of the polypeptide are rejoined.

• Unlike proteolytic processing, protein selfsplicing is an autocatalytic process, which
proceeds by itself without the participation of enzymes.
• The excised peptide appears to eliminate itself from the protein by a mechanism
similar to that used in the processing of some RNA molecule.
• In vertebrate cells, the processing of some proteins includes self-cleavage, but the
subsequent ligation step is absent. One such protein is Hedgehog, a membrane bound
signaling molecule that is critical to a number of developmental processes.

Specificity and Affinity of Protein–Ligand Binding
Depend on Molecular Complementarity
• Two properties of a protein characterize its interaction with ligands.
• Specificity refers to the ability of a protein to bind one molecule in preference to other molecules.
• Affinity refers to the strength of binding.
• Both the specificity and the affinity of a protein for a ligand depend on the structure of the ligand-
binding site, which is designed to fit its partner like a mold.
• For high-affinity and highly specific interactions to take place, the shape and chemical surface of the
binding site must be complementary to the ligand molecule, a property termed molecular
complementarity.
• The ability of proteins to distinguish different molecules is perhaps most highly developed in the
blood proteins called antibodies, which animals produce in response to antigens, such as infectious
agents (e.g., a bacterium or a virus), and certain foreign substances (e.g., proteins or polysaccharides
in pollens).
• The presence of an antigen causes an organism to make a large quantity of different antibody
proteins, each of which may bind to a slightly different region, or epitope, of the antigen.

Immunology
is a branch of biology and medicine[1]
that covers the study of immune systems[2]
in all organisms.
It was Mechnikov who first observed the phenomenon of phagocytosis,[9]
in which the body defends
itself against a foreign body. The system based on atibody-antigen interaction machanisim.
• All antibodies are Y-shaped molecules formed from two identical heavy chains and two
identical light chains (Figure 3-15a). Each arm of an antibody molecule contains a single
light chain linked to a heavy chain by a disulfide bond.
• Near the end of each arm are six highly variable loops, called complementarity-
determining regions (CDRs), which form the antigen-binding sites. The sequences of the
six loops are highly variable among antibodies, making them specific for different
antigens.
• The interaction between an antibody and an epitope in an antigen is complementary
in all cases; that is, the surface of the antibody’s antigen-binding site physically matches
the corresponding epitope like a glove (Figure 3-15b).
• The intimate contact between these two surfaces, stabilized by numerous noncovalent
bonds, is responsible for the exquisite binding specificity exhibited by an antibody.

• Antibody, also called immunoglobulin, a protective protein produced by
the immune system in response to the presence of a foreign substance,
called an antigen.
• Antibodies recognize and latch onto antigens in order to remove them from
the body.
• A wide range of substances are regarded by the body as antigens, including
disease-causing organisms and toxic materials such as insect venom.
• When an alien substance enters the body, the immune system is able
to recognize it as foreign because molecules on the surface of the
antigen differ from those found in the body.

• To eliminate the invader, the immune system calls on a number
of mechanisms, including one of the most important—antibody
production.
• Antibodies are produced by specialized white blood cells called
B lymphocytes (or B cells).
• When an antigen binds to the B-cell surface, it stimulates the
B cell to divide and mature into a group of identical cells called a
clone.
• The mature B cells, called plasma cells, secrete millions of
antibodies into the bloodstream and lymphatic system.

• As antibodies circulate, they attack and neutralize antigens that are
identical to the one that triggered the immune response.
• Antibodies attack antigens by binding to them. The binding of an
antibody to a toxin, for example, can neutralize the poison simply by
changing its chemical composition; such antibodies are called antitoxins.
• By attaching themselves to some invading microbes, other antibodies can
render such microorganisms immobile or prevent them from penetrating
body cells.
• In other cases the antibody-coated antigen is subject to a chemical
chain reaction with complement, which is a series of proteins found in
the blood.

• The complement reaction either can trigger the lysis (bursting)
of the invading microbe or can attract microbe-killing scavenger
cells that ingest, or phagocytose, the invader.
• Once begun, antibody production continues for several days
until all antigen molecules are removed.
• Antibodies remain in circulation for several months, providing
extended immunity against that particular antigen.

• B cells and antibodies together provide one of the most important
functions of immunity, which is to recognize an invading antigen and
to produce a tremendous number of protective proteins that scour
the body to remove all traces of that antigen.
• Collectively B cells recognize an almost limitless number of antigens;
however, individually each B cell can bind to only one type of antigen.
• B cells distinguish antigens through proteins, called antigen receptors
, found on their surfaces. An antigen receptor is basically an antibody
protein that is not secreted but is anchored to the B-cell membrane.

• All antigen receptors found on a particular B cell are identical, but receptors
located on other B cells differ.
• Although their general structure is similar, the variation lies in the area that
interacts with the antigen—the antigen-binding, or antibody-combining, site.
• This structural variation among antigen-binding sites allows different B cells
to recognize different antigens.
• The antigen receptor does not actually recognize the entire antigen; instead it
binds to only a portion of the antigen’s surface, an area called the
antigenic determinant or epitope.
• Binding between the receptor and epitope occurs only if their structures are
complementary. If they are, epitope and receptor fit together like two pieces of
a puzzle, an event that is necessary to activate B-cell production of antibodies.

• Antibodies are grouped into five classes according to their
constant region.
• Each class is designated by a letter attached to an abbreviation
of the word immunoglobulin: IgG, IgM, IgA, IgD, and IgE.
• The classes of antibody differ not only in their constant region
but also in activity.
• For example, IgG, the most common antibody, is present mostly
in the blood and tissue fluids, while IgA is found in the mucous
membranes lining the respiratory and gastrointestinal tracts.

Enzymes Are Highly Efficient and Specific
Catalysts
• In contrast with antibodies, which bind and simply present their ligands to other components of the
immune system, enzymes promote the chemical alteration of their ligands, called substrates.
• Almost every chemical reaction in the cell is catalyzed by a specific enzyme. Like all catalysts,
enzymes do not affect the extent of a reaction, which is determined by the change in free energy G
between reactants and products.
• For reactions that are energetically favorable (G), enzymes increase the reaction rate by lowering
the activation energy.
• Two striking properties of enzymes enable them to function as catalysts under the mild conditions
present in cells:
• their enormous catalytic power
• their high degree of specificity.
• The immense catalytic power of enzymes causes the rates of enzymatically catalyzed reactions to
be 106–1012 times that of the corresponding uncatalyzed reactions under otherwise similar
conditions.
• The exquisite specificity of enzymes—their ability to act selectively on one substrate or a small
number of chemically similar substrates—is exemplified by the enzymes that act on amino acids.

Regulation of catalytic activity
• The most common type of control occurs when a molecule other than a substrate
specifically binds to an enzyme at a special regulatory site outside of the active
site, altering the rate at which the enzyme converts its substrates to products.
• In feedback inhibition, an enzyme acting early in a reaction pathway is inhibited
by a late product of that pathway. Thus, whenever large quantities of the final
product begin to accumulate, the product binds to an earlier enzyme and slows
down its catalytic action, limiting further entry of substrates into that reaction
pathway (figure 4–34).
• Where pathways branch or intersect, there are usually multiple points of control
by different final products, each of which works to regulate its own synthesis
(figure 4–35). Feedback inhibition can work almost instantaneously, and is rapidly
reversed when product levels fall.

Allosteric enzymes have Binding Sites That influence one
another
• The regulatory molecule often has a shape that is totally different from the shape of the enzyme’s preferred
substrate and it was termed as allostery (from the Greek allo, “other,” and stere, “solid” or “shape”).
• Many enzymes must have at least two different binding sites on their surface
• the active site that recognizes the substrates
• one or more sites that recognize regulatory molecules.
• Furthermore, the substrate and regulatory sites must somehow “communicate” in a way that allows the
catalytic events at the active site to be influenced by the binding of the regulatory molecule at its separate
site.
• The interaction between sites that are located on separate regions of a protein molecule is now known to
depend on conformational changes
• in the protein: binding at one of the sites causes a shift in the protein’s structure from one folded shape to a
slightly different folded shape.
• Many enzymes have two conformations that differ in activity, each stabilized by the binding of different
ligands. During feedback inhibition, for example, the binding of an inhibitor at one site on the protein causes
the protein to shift to a conformation in which its active site—located elsewhere in the protein—becomes less
accommodating to the substrate molecule (figure 4–36).

Protein its shape ,structure and functions

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