Structure of Proteins

Proteins are polymers of amino acids, and their three-dimensional structure depends mainly on the sequence of amino acids (the residues) making up the chain. This structure is conventionally described at four hierarchical levels: primary, secondary, tertiary and quaternary.

1. Primary structure. Proteins are polypeptide chains made up of amino acids connected through peptide bonds; the relative arrangement -- the exact order -- of the amino acids along this chain is called the primary structure of the protein. Knowing the primary structure is essential, because even a single substitution in this sequence has the potential to alter the protein's overall folded structure and, with it, its biological function.

2. Secondary structure. The amino acids along the polypeptide chain fold into highly regular, repeating local shapes (sub-structures) through hydrogen bonding between the carbonyl oxygen (C=O) of one backbone amide and the amine hydrogen (-NH) of a neighbouring backbone amide. The two most common secondary-structure sub-structures are the α-helix and β-strands (or β-sheets). In the α-helix, the amino acids coil into a right-handed helical (spiral) structure, stabilised by a hydrogen bond between the carbonyl oxygen of one residue (the nth residue) and the amino hydrogen of the residue four positions further along the chain (the (n+4)th residue); the side chains of the residues all point outward from the helix. Each turn of the helix contains about 3.6 residues and spans about 5.4 Å along the helix axis. The amino acid proline cannot adopt this hydrogen-bonding pattern because of its rigid, cyclic side chain, so it produces a kink wherever it occurs in a helix and is often called a helix breaker. In a β-strand, by contrast, the peptide chain is extended rather than coiled; hydrogen bonds form between the backbone carbonyl group of one such strand and the backbone amino group of an adjacent strand, and the resulting side-by-side arrangement of several strands is called a β-sheet.

3. Tertiary structure. The secondary-structure elements (the α-helices and β-sheets) themselves fold further into an overall three-dimensional arrangement, and this next level of folding is called the tertiary structure of the polypeptide (protein). Tertiary structure is stabilised by interactions between the side chains (R groups) of the amino acids scattered throughout the chain -- specifically disulphide bridges between cysteine residues, electrostatic interactions, hydrophobic interactions, hydrogen bonds, and van der Waals interactions, all acting together to lock the chain into its functional 3-D shape. …