The Component Polypeptide Chains of Bovine Insulin Nucleate or Inhibit Aggregation of the Parent Protein in a Conformation-dependent Manner

Abstract

Amyloid fibrils are typically rigid, unbranched structures with diameters of ∼10 nm and lengths up to several micrometres, and are associated with more than 20 diseases including Alzheimer's disease and type II diabetes. Insulin is a small, predominantly α-helical protein consisting of 51 residues in two disulfide-linked polypeptide chains that readily assembles into amyloid fibrils under conditions of low pH and elevated temperature. We demonstrate here that both the A-chain and the B-chain of insulin are capable of forming amyloid fibrils in isolation under similar conditions, with fibrillar morphologies that differ from those composed of intact insulin. Both the A-chain and B-chain fibril..