Title
Atomic structure and hierarchical assembly of a cross-β amyloid fibril
Date Issued
02 April 2013
Access level
open access
Resource Type
journal article
Author(s)
Fitzpatrick A.W.P.
Debelouchina G.T.
Clare D.K.
Caporini M.A.
Bajaj V.S.
Jaroniec C.P.
Wang L.
Ladizhansky V.
Müller S.A.
MacPhee C.E.
Waudby C.A.
Mott H.R.
De Simone A.
Knowles T.P.J.
Saibil H.R.
Vendruscolo M.
Orlova E.V.
Griffin R.G.
Dobson C.M.
Massachusetts Institute of Technology
Abstract
The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale-including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy-we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.
Start page
5468
End page
5473
Volume
110
Issue
14
Language
English
OCDE Knowledge area
Ingeniería, Tecnología Física atómica, molecular y química
Scopus EID
2-s2.0-84875871051
PubMed ID
Source
Proceedings of the National Academy of Sciences of the United States of America
ISSN of the container
00278424
Sponsor(s)
National Institute of Biomedical Imaging and Bioengineering - R01EB003151
Sources of information: Directorio de Producción Científica Scopus