Structure of Proteins: Primary to Quaternary Organisation

A functional protein is not simply a random tangle of amino acids but a precisely folded molecule whose three-dimensional shape is described at four distinct, hierarchical levels of organisation.

The primary structure of a protein is the linear sequence in which its amino acids are joined, one after another, by peptide bonds along the polypeptide backbone. This sequence is unique to each protein, is specified directly by the genetic code, and is conventionally written starting from the free amino (N-terminal) end and ending at the free carboxyl (C-terminal) end. Even a single substitution in this sequence -- as in the single amino-acid change that produces sickle-cell haemoglobin -- can profoundly alter the protein's shape and function.

The secondary structure refers to regular, repeating local folding patterns that arise from hydrogen bonding between the backbone -NH and C=O groups of amino acids that lie close together along the chain. The two most common secondary structures are the alpha-helix, a right-handed spiral coil stabilised by hydrogen bonds between every fourth amino acid (found extensively in fibrous proteins such as keratin), and the beta-pleated sheet, in which extended, zig-zag polypeptide strands lie side by side and are held together by hydrogen bonds between adjacent strands (as in silk fibroin).

The tertiary structure describes the overall three-dimensional folding of a single polypeptide chain into its compact, biologically functional shape. This folding is stabilised by a range of additional interactions beyond simple hydrogen bonding -- ionic bonds between oppositely charged side chains, disulphide bridges formed by the oxidation of two cysteine side chains, and hydrophobic interactions in which non-polar side chains cluster away from the surrounding water toward the molecule's interior. The tertiary structure of a protein such as myoglobin creates the specific pocket needed for its biological activity.

The quaternary structure applies only to proteins built from more than one polypeptide chain (subunit, or protomer), and describes how these separate chains associate to form the final, functional multi-subunit protein. Haemoglobin is the classic example: it is assembled from four separate polypeptide subunits -- two identical alpha chains and two identical beta chains -- each folded into its own tertiary structure and each carrying its own haem group, held together as one functional unit. …