The structure of insulin is different among different species of animals. However, essentially it is a protein chain that is similar in many ways among animals.
Human insulin is closest in structure and function with cow (bovine) or pig (porcine) insulin. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one.
Insulin from some invertebrates and even fishes can be clinically useful in humans as they possess several similarities.
Normal insulin that is biologically active is monomeric or exists as a single molecule. It has two long amino acid chains or polypeptide chains. The chains are chain A with 21 amino acids and chain B with 30 amino acids.
Two disulfide bridges (residues A7 to B7, and A20 to B19) covalently connect the chains, and chain A contains an internal disulfide bridge (residues A6 to A11). These joints are similar in all mammalian forms of insulin.
When secreted insulin joins in two’s to form dimmers and then in six’s to form hexamers. This combination takes place in the presence of zinc.
The peptide chains then form 2 dimensional and three dimensional forms. Each of these 3-dimensional structures have three helices and three conserved disulfide bridges. This is a basic fold. This basic fold is present in all members of the insulin peptide family.
At the core or center of the molecules is a hydrophobic or “water-hating” or water repellent area. These cluster of hydrophobic residues in the center contributes to protein stability. Stability is also lent by the disulfide bridges.
Surrounding its core, the monomer has two extensive nonpolar surfaces. One of them is a flat one that is aromatic and gets buried when there is a dimer formation. The other surface is more extensive and disappears when a hexamer is formed. This is called the quaternary structure of insulin.
Structure at synthesis
In the beta cells of the pancreas, the insulin molecule is originally produced as a single molecule (preproinsulin) composed of 110 amino acids. It passes through the endoplasmic reticulum and 24 amino acids ("the signal peptide") are removed by enzyme action from one end of the chain, leaving another form (pro-insulin) behind.
The proinsulin folds and binds to give the molecule its final structure. Then the proinsulin passes into vesicles budded off from the Golgi body.
Thereafter the middle section ("the C chain") of 33 amino-acids is removed by the action of the enzymes prohormone convertase 1 and 2, converting it into the final structure with 2 chains, A and B. Further 2 amino acids are removed by another enzyme carboxypeptidase E.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)