Molecular basis for insulin fibril assembly

• DOI: 10.1073/pnas.0910080106
• Publication Date: 2009-10-29T02:17:15Z
• Authors: Magdalena I. Ivanova; Stuart A. Sievers; Michael R. Sawaya; Joseph S. Wall; David Eisenberg
• Keywords: Fiber diffraction; Amyloid (mycology); Microcrystalline; Morphology

In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that segment B-chain with sequence LVEALYL is smallest both nucleates and inhibits fibrillation full-length in a molar ratio–dependent manner, suggesting this central to cross-β spine fibril. isolation from rest protein, forms microcrystalline aggregates fibrillar morphology, structure which we determined 1 Å resolution. The segments stacked into pairs tightly interdigitated β-sheets, each pair displaying dry steric zipper interface typical amyloid-like fibrils. This leads model for human consistent electron microscopic, x-ray fiber diffraction, biochemical studies.