John J. Berzelius (1838) first coined the term ‘protein’ (Gr. proteios — of the first rank) to stress the importance of this class of polymers.
Proteins are the macromolecules composed of one or more polypeptide chains, each of which is a mixed polymer of L-a-amino acid residues joined end-to-end by peptide bonds.
Monomeric protein consists of single polypeptide chain, e.g., lysozyme, myoglobin. The oligomeri c or multimeric protein consists of 2 or more polypeptide chains, each of which is called a protomere or subunit. Rubisco consists of 24 polypeptides, hemoglobin (Hb) is a tetrameric consists of two a-chains and two β- chains, immunoglobulins consists of 2 H-chains and 2H-chains etc.
Structure of Proteins:
A polypeptide chain is synthesized on the ribosome as a linear sequence of amino acids. Just after the synthesis, the newly synthesized (nascent) polypeptide folds into a specific three dimensional shape called conformation. The conformation adopted by polypeptide to perform the biological activity is called native conformation.
Previously, it was thought that proteins fold spontaneously to attain their native states. Recent studies revealed that chaperone proteins accelerate the folding process of nescent polypeptides into their native conformations. The deficiencies of chaperone proteins cause diseases due to incorrect folding of proteins. For example, in Alzheimer disease the amyloid plaques develop due to protein clumping in brain cells.
Levels of Protein Structure:
The structure of protein can be described in terms of four levels of organizations: Primary, Secondary, Tertiary and Quaternary. Recent studies revealed two additional levels of protein organization i.e. Super- secondary structures or motifs and domains.
A. Primary (1°) Structure:
Primary structure of a protein means the sequences amino acid residues of its polypeptide chain (s) which read in N-terminus → C-terminus direction. It is the 1st level of organization of protein determined by the codons of mRNA or cistron of DNA. The 1° structure is stabilized by the peptide bonds as well as and disulfide bonds between cysteine residues, if there are any.
Frederick Sanger (1953) first determined the 1° structure of bovine insulin. Now, the 1° structure of a polypeptide is determined by an automated device called spinning cup sequenator, developed by Pehr Edman and Geoffrey Begg.
B. Secondary (2°) structure:
Protein 2° structure refers to the spatial arrangement of backbone atoms of polypeptides without considering the conformations of side chains. The common types of secondary structures are α-helix and β-pleated sheet. The type of 2° structure of a polypeptide depends upon its amino acid composition. The α-helix formation is favoured by alanine, leucine, glutamate and methionine residues, whereas β- sheet is favoured by valine, isoleucine and tyrosine residues.
(i) α-Helix:
The backbone atoms of a polypeptide chain tightly coiled in a right-handed manner to form many rod-like structures at intervals called a-helices. For example, the single polypeptide chain of myoglobin contains 8 helices. On the outside of helix the side chains extend outward in a helical manner.
The length of each helix usually varies from 1.7-4.0 nm. In a α-helix, 3.6 amino acid residues present per turn covering a distance (pitch) of 0.54 nm (5.4A). The a-helix is stabilized by hydrogen bonds between the CO group of one amino acid with the NH group of fourth amino acid away. Glycine and proline are often called helix breakers because of their inability to form hydrogen bonds.
(ii) β- pleated sheet:
About 2-15 polypeptide chains come together to form a β-pleated sheet. The β-pleated sheet is stabilized by hydrogen bonds between CO- and NH groups in different polypeptide chains; β- pleated sheet is of 2 types –
Parallel β-sheet – Adjacent chains run in the same direction e.g. β-keratin.
Antiparallel β-sheet – Adjacent chains own in opposite direction e.g. silk fibroin.
Super Secondary Structures:
Two or more secondary structures often aggregate to form a complex structural unit called super secondary structure or motif. Some common motifs are as follows:
C. Tertiary (3°) Structures:
Protein tertiary structure refers to the 3-D structure of an entire polypeptide showing the folding of secondary and super secondary structures to form a compact globular structure. In case of a large polypeptide, that consists of more than – 200 residues form two or more globular units called domains. (A domain is a compact, globular, structurally independent unit that connects with other such unit by peptide backbone). The 3° structure is stabilized by hydrogen bonds, ionic bonds, hydrophobic interactions, Vander Walls force, and London dispersion forces and disulfide bonds if present.
D. Quaternary (4°) Structure:
It is the fourth level of structural organization exhibited only in oligomeric proteins. A protein’s quaternary structure refers to the spatial arrangement of its polypeptide subunits or protomers. In a 4° structure the subunits may or may not be identical, and stabilized by non covalent bonds, e.g., Haemoglobin.
Protein denaturation:
Any partial unfolding or change in 3-D shape that brings a native state of a protein into random coil is called denaturation. But, the separation of subunits in a 4° structure is called dissociation. Proteins are denatured by variety of conditions such as high temperature, variation in pH and ionic concentrations; addition of detergents etc. When the normal condition is established smaller denatured proteins refold spontaneously into its native conformation. This is called renaturation but larger protein can rarely renaturate (fold spontaneously) to its native state.