title: Atomic structure and hierarchical assembly of a cross-β amyloid fibril.
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.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
authors.forename: Anthony W P
authors.initials: AW
authors.lastname: Fitzpatrick
authors.forename: Galia T
authors.initials: GT
authors.lastname: Debelouchina
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Bayro
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Clare
authors.forename: Marc A
authors.initials: MA
authors.lastname: Caporini
authors.forename: Vikram S
authors.initials: VS
authors.lastname: Bajaj
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Jaroniec
authors.forename: Luchun
authors.initials: L
authors.lastname: Wang
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ladizhansky
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Müller
authors.forename: Cait E
authors.initials: CE
authors.lastname: MacPhee
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Waudby
authors.forename: Helen R
authors.initials: HR
authors.lastname: Mott
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Simone
authors.forename: Tuomas P J
authors.initials: TP
authors.lastname: Knowles
authors.forename: Helen R
authors.initials: HR
authors.lastname: Saibil
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
authors.forename: Elena V
authors.initials: EV
authors.lastname: Orlova
authors.forename: Robert G
authors.initials: RG
authors.lastname: Griffin
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D017348:Microscopy, Electron, Scanning Transmission; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid