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Biochemistry. 2012 May 15;51(19):3957-9. doi: 10.1021/bi300350p. Epub 2012 May 7.

Structural dynamics of the amyloid β-protein monomer folding nucleus.

Author information

1
Department of Neurology, University of California, Los Angeles, CA 90095, USA.

Abstract

Alzheimer's disease (AD) is linked to the aberrant assembly of the amyloid β-protein (Aβ). The (21)AEDVGSNKGA(30) 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.

PMID:
22551351
PMCID:
PMC3362201
DOI:
10.1021/bi300350p
[Indexed for MEDLINE]
Free PMC Article

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