Insulin keeps racking up firsts in the history of protein science
Insulin was the first peptide hormone ever found, the first protein to have its full amino acid sequence read, the first protein made by chemical synthesis and the first produced with recombinant DNA. And a pair of venomous sea snails turned it into a weapon long before any laboratory touched it.
The discoveries came in a steady procession. At the University of Toronto in 1921, Frederick Banting and Charles Best, working in John Macleod's laboratory, isolated it from dog pancreas. Frederick Sanger worked out its amino acid order in 1951, and Dorothy Hodgkin determined its crystal structure in 1969. It now sits on the World Health Organization's Model List of Essential Medicines.
Scientists had expected hormones to be small molecules, so insulin's size came as a surprise. Human insulin has 51 amino acids and weighs 5808 daltons, split between an A-chain of 21 residues and a B-chain of 30, stitched together by two disulfide bridges with a third inside the A-chain. The body stores it in clusters of six held around zinc atoms, while the working form is a single unit. It begins as a longer precursor of 110 amino acids, which is trimmed in stages, including removal of a middle segment called the C-peptide.
The sequence barely changes across animals. Cattle insulin differs from ours at three positions and pig insulin at just one, which is why pig insulin was widely used for type 1 diabetes before recombinant human insulin became available in bulk. Some fish insulin works in humans too, and the molecule's ancestry may reach back more than a billion years, with related proteins in fungi and single-celled organisms. The name comes from the Latin for island, after the pancreatic islets whose beta cells make it.
Two cone snails, Conus geographus and Conus tulipa, hunt small fish with venom that includes modified insulin. Their version resembles fish insulin more than the snails' own, and it slows prey by dragging down its blood sugar.
Source: Insulin
