Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid peptide

Biophys J. 2006 Jun 15;90(12):4618-29. doi: 10.1529/biophysj.105.076927. Epub 2006 Mar 24.

Abstract

We report investigations of the morphology and molecular structure of amyloid fibrils comprised of residues 10-40 of the Alzheimer's beta-amyloid peptide (Abeta(10-40)), prepared under various solution conditions and degrees of agitation. Omission of residues 1-9 from the full-length Alzheimer's beta-amyloid peptide (Abeta(1-40)) did not prevent the peptide from forming amyloid fibrils or eliminate fibril polymorphism. These results are consistent with residues 1-9 being disordered in Abeta(1-40) fibrils, and show that fibril polymorphism is not a consequence of disorder in residues 1-9. Fibril morphology was analyzed by atomic force and electron microscopy, and secondary structure and inter-side-chain proximity were probed using solid-state NMR. Abeta(1-40) fibrils were found to be structurally compatible with Abeta(10-40): Abeta(1-40) fibril fragments were used to seed the growth of Abeta(10-40) fibrils, with propagation of fibril morphology and molecular structure. In addition, comparison of lyophilized and hydrated fibril samples revealed no effect of hydration on molecular structure, indicating that Abeta(10-40) fibrils are unlikely to contain bulk water.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acids / chemistry*
  • Amyloid / chemical synthesis*
  • Amyloid / ultrastructure*
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / ultrastructure*
  • Binding Sites
  • Dimerization
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / ultrastructure
  • Protein Binding
  • Protein Conformation

Substances

  • Amino Acids
  • Amyloid
  • Amyloid beta-Peptides
  • Multiprotein Complexes