American Chemical Society
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Structural Dynamics of the Amyloid β-Protein Monomer Folding Nucleus

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journal contribution
posted on 2012-05-15, 00:00 authored by Robin Roychaudhuri, Mingfeng Yang, Margaret M. Condron, David B. Teplow
Alzheimer’s disease (AD) is linked to the aberrant assembly of the amyloid β-protein (Aβ). The 21AEDVGSNKGA30 segment, Aβ(21–30), forms a turn that acts as a monomer folding nucleus. Amino acid substitutions within this nucleus cause familial forms of AD. To determine the biophysical characteristics of the folding nucleus, we studied the biologically relevant acetyl-Aβ(21–30)-amide peptide using experimental techniques (limited proteolysis, thermal denaturation, urea denaturation followed by pulse proteolysis, and electron microscopy) and computational methods (molecular dynamics). Our results reveal a highly stable foldon and suggest new strategies for therapeutic drug development.