|
Proteins are polymers of amino acids. Each amino acid has the same fundamental structure, differing only in the side-chain, designated the R-group. The carbon atom to which the amino group, carboxyl group, and side chain (R-group) are attached is the alpha carbon (Ca).
|
|
Structures of amino acids, with their R-groups in blue, are shown below with their three-letter and one-letter abbreviated names. Glycine has just a hydrogen atom in place of an R-group. At physiological pH, some amino acid R-groups are charged, because of dissociation or association of a proton by, e.g., a carboxyl or amino group. Note that histidine is shown charged, but its pK is close to the physiological range. Some side-chain groups that are uncharged at the near-neutral pH of the cytosol or extracellular space, may dissociate or gain a proton in the microenvironment of an enzyme active site.
Protein structure is studied under four different levels namely Primary structure, Secondary structure, Tertiary structure and Quaternary structure.
|
Peptide bonds link amino acid residues within proteins. The sequence of covalently linked amino acids is known as the primary structure of a protein.
The reaction by which two amino acids are joined in a peptide bond, with elimination of H2O, is represented at right. A protein is a polypeptide, a linear polymer of many amino acids, linked by peptide bonds.
|
|
|
The peptide linkages, along with the a-carbon atoms to which R-groups are attached, form the protein backbone, with sequence NCCNCCNCCNCC... |
|
|
Protein Secondary Structure: Segments of polypeptides often fold locally into stable structures that include a-helices and b-pleated sheets. a-Helix. In an a-helix (alpha helix), the polypeptide backbone follows a helical path. There are 3.6 amino acid residues per turn of the helix. Some protein domains assume other helical structures, but the a-helix is most common.
|
|
|
An a-helix is stabilized by hydrogen bonds between backbone amino and carbonyl groups and those in the next turn of the helix, represented as N-H····O=C. The hydrogen and oxygen atoms are attracted to one another because the H atom carries a partial positive charge and the O atom carries a partial negative charge, due to unequal sharing of electrons in N-H and O=C bonds.
|
|
|
In an a-helix, the amino acid R-groups protrude out from the helically coiled polypeptide backbone. The surface of an a-helix largely consists of the R-groups of amino acid residues. |
|
|
Some amino acids have a greater tendency to be found within an a-helix. The amino acid proline tends to interrupt an a-helix. Its fused ring, which includes the a-carbon and the peptide-forming amino N, prevents the polypeptide backbone from assuming a conformation compatible with an a-helix in the vicinity of a proline.
|
|
Beta pleated sheets:
Another common secondary structure is the b sheet (beta sheet). In a b sheet, strands of protein lie adjacent to one another, interacting laterally via H bonds between backbone carbonyl oxygen and amino H atoms. The strands may be parallel (N-termini of both strands at the same end) or antiparallel.
Because of the tetrahedral nature of carbon bonds, a b-sheet is puckered, leading to the designation pleated sheet.
R groups of amino acids in a b-strand alternately point to one side or the other of a b-strand. Hence every other amino acid is exposed on one side or the other of a b-sheet.
|
A common structural motif, the b-barrel, is equivalent to a b-sheet that is rolled up to form a cylinder. An example of a protein that consists mainly of a b-barrel is the bacterial channel porin.
In some cases, a b-barrel may be partly flattened, to form what is called a b-clam structure. |
|
|
Other common folding motifs involve combinations of a-helices and b-strands. One example is the a,b-barrel, explored elsewhere in an exercise on Triose Phosphate Isomerase (TIM).
|
|
Tertiary protein structure:
It refers to the complete three dimensional folding of a protein. Stabilization of a protein's tertiary structure may involve interactions between amino acids located far apart along the primary sequence. These may include:
Interactions with the aqueous solvent, known as the hydrophobic effect results in residues with non-polar side-chains typically being buried in the interior of a protein. Conversely, polar amino acid side-chains tend to on the surface of a protein where they are exposed to the aqueous milieu. There are, however, many exceptions in which polar residues are buried or non-polar residues exposed on the surface of a protein. Such atypical locations might be stabilized, e.g., by interaction of amino acid side-chains with enzyme prosthetic groups or other ligands, by interactions between amino acid side-chains, or by association of proteins with lipid membranes, etc.
|
Many proteins have a modular design with multiple distinct domains resulting from gene fusion events during evolution. A domain with a particular structure and function may be part of the structure of several otherwise distinct proteins. For example, an enzyme's primary structure may include a segment that folds to produce an active site with particular catalytic activity, plus other segments that may mediate regulation of the enzyme or binding of the enzyme to a membrane.
|
|
|
Quaternary protein structure :
It refers to the regular association of two or more polypeptide chains to form a complex. A multi-subunit protein may be composed of two or more identical polypeptides, or it may include different polypeptides. Quaternary structure tends to be stabilized mainly by weak interactions between residues exposed on surfaces polypeptides within a complex.
A multimeric complex may be important to enzyme activity, e.g., in cases in which an active site is formed by residues from more than one polypeptide subunit, or when adjacent active sites may be involved sequentially in catalysis of a complex reaction. Regulation of functional activity may involve cooperative interactions among protein subunits in a complex. |
|
