Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science

Citation
Ha. Lashuel et al., Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science, J AM CHEM S, 122(22), 2000, pp. 5262-5277
Citations number
95
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis",Chemistry
Journal title
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN journal
0002-7863 → ACNP
Volume
122
Issue
22
Year of publication
2000
Pages
5262 - 5277
Database
ISI
SICI code
0002-7863(20000607)122:22<5262:PFRAFF>2.0.ZU;2-G
Abstract
Deciphering the mechanism(s) of beta-sheet mediated self-assembly is essent ial for understanding amyloid fibril formation and for the fabrication of p olypeptide materials. Herein, we report a simple peptidomimetic that self-a ssembles into polymorphic beta-sheet quaternary structures including protof ilaments, filaments, fibrils, and ribbons that are reminiscent of the highl y ordered structures displayed by the amyloidogenic peptides A beta, calcit onin, and amylin. The distribution of quaternary structures can be controll ed by and in some cases specified by manipulating the pH, buffer compositio n, and the ionic strength. The ability to control beta-sheet-mediated assem bly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as wel l as far-UV circular dichroism and FT-IR spectroscopy demonstrate that link ed secondary and quaternary structural changes mediate peptidomimetic self- assembly. Electron and atomic force microscopy reveal that peptidomimetic a ssembly involves numerous quaternary structural intermediates that appear t o self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and t he final quaternary structure(s) afforded should prove to be particularly u seful in deciphering the quaternary structural requirements for amyloid fib ril formation and for the construction of noncovalent macromolecular struct ures.