Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid peptide.
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.
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Anant K
AK
Paravastu
Aneta T
AT
Petkova
Robert
R
Tycko
D000596:Amino Acids / Q000737:chemistry*; D000682:Amyloid / Q000138:chemical synthesis* / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D019281:Dimerization; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation
D000596:Amino Acids; D000682:Amyloid; D016229:Amyloid beta-Peptides; D046912:Multiprotein Complexes