2009/10/28 by Magdalena I. Ivanova, Stuart A. Sievers, M.R. Sawaya +2 · 2 citations
Medicine · Biochemistry, Genetics and Molecular Biology · Materials Science · #Alzheimer's disease research and treatments #Protein Structure and Dynamics #Enzyme Structure and Function
paper · doi:10.1073/pnas.0910080106
openalex publication_date 2009/10/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that the segment of the insulin B-chain with sequence LVEALYL is the smallest segment that both nucleates and inhibits the fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting that this segment is central to the cross-beta spine of the insulin fibril. In isolation from the rest of the protein, LVEALYL forms microcrystalline aggregates with fibrillar morphology, the structure of which we determined to 1 A resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated beta-sheets, each pair displaying the dry steric zipper interface typical of amyloid-like fibrils. This structure leads to a model for fibrils of human insulin consistent with electron microscopic, x-ray fiber diffraction, and biochemical studies.