Water Penetration into a Dry Amyloid Fibril

Abstract

Amyloid formation is a key feature of Alzheimer's disease. Amyloid is composed of 39-42 residue proteins that have aggregated into fibrils. Experimental and theoretical studies of amyloid fibril structure have suggested a model in which two different parallel in-register beta sheets pack against each other with a dry interface. However, recent 2D-IR results have detected water molecules within a mature folded fibril. To explore this discrepancy, we created a molecular dynamics simulation of a dry amyloid fibril in water. We observed that water enters the space between beta sheets through hydrogen bonding interactions with the side chain or main chain of Asp23, and the main chain carbonyl group of Gly25. The involvement of main chain carbonyl groups in water transport down the interior of an amyloid fibril suggests that individual hydrogen bonds comprising the beta sheet may form and transiently unform, facilitating events like water transport while maintaining overall fibril structure.