Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate.

ABSTRACT: Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique β-strand structure distinct from the conventional amyloid β-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated interm

SUBMITTER: Rodriguez Camargo DC 

PROVIDER: S-EPMC5706959 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature