A folding transition underlies the emergence of membrane affinity in amyloid-β

Phys Chem Chem Phys. 2013 Nov 28;15(44):19129-33. doi: 10.1039/c3cp52732h.

Abstract

Small amyloid-β (Aβ) oligomers have much higher membrane affinity compared to the monomers, but the structural origin of this functional change is not understood. We show that as monomers assemble into small n-mers (n < 10), Aβ acquires a tertiary fold that is consistent with the mature fibrils. This is an early and defining transition for the aggregating peptide, and possibly underpins its altered bioactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Fluorescein / chemistry
  • Fluorescence Resonance Energy Transfer
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphatidylcholines / chemistry
  • Protein Folding
  • Protein Structure, Secondary

Substances

  • 1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Phosphatidylcholines
  • amyloid beta-protein (1-40)
  • Fluorescein