title: Structural dynamics of the amyloid β-protein monomer folding nucleus.
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.
authors.affiliation: Department of Neurology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Roychaudhuri
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Yang
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Condron
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D055550:Protein Stability; D059748:Proteolysis
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C501831:amyloid beta-protein (21-30)