NIH R01 · 2024
Conformational heterogeneity and alpha-sheet: Determinants of toxicity in Abeta variants
Amyloid diseases involve conformational changes and aggregation of normally soluble peptides and proteins. As these proteins change begin to misfold and aggregate they pass through a toxic soluble oligomer stage and then they ultimately form insoluble fibrils. We have spent many years characterizing the early events in this progression, and have observed a common structure form among multiple amyloid-associated peptides and proteins despite distinct primary and tertiary structure. The structure we “discovered”, which we call α-sheet, while rare in normal proteins, has been observed experimentally, and short stretches of α-strand are present in the Protein Data Bank. We embarked on an…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.