Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly

• Published in: Nature structural & molecular biology Vol. 27; no. 11; pp. 1048 - 1056
• Main Authors: Gallardo, Rodrigo, Iadanza, Matthew G., Xu, Yong, Heath, George R., Foster, Richard, Radford, Sheena E., Ranson, Neil A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2020; Nature Publishing Group
• Subjects: 101/28; 14/3; 631/45/470/2284; 631/535/1258/1259; Age; Agglomeration; Amylin; Amyloid - chemistry; Amyloid - genetics; Amyloid - ultrastructure; Assembly; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Conformation; Cryoelectron Microscopy; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Fibrils; Humans; Islet Amyloid Polypeptide - chemistry; Islet Amyloid Polypeptide - genetics; Islet Amyloid Polypeptide - ultrastructure; Life Sciences; Membrane Biology; Models, Molecular; Mutation; Point Mutation; Protein Conformation; Protein Structure; β-Amyloid

Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G mutation in amylin is associated with early-onset T2D. Here we report cryo-EM structures of amyloid fibrils...