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The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

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posted on 2023-06-09, 00:13 authored by A E Langkilde, K L Morris, Louise SerpellLouise Serpell, D I Svergun, B Vestergaard
Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods.

History

Publication status

  • Published

File Version

  • Published version

Journal

Acta Crystallographica Section D: Biological Crystallography

ISSN

1399-0047

Publisher

International Union of Crystallography

Issue

4

Volume

71

Page range

882-895

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-02-05

First Open Access (FOA) Date

2016-02-05

First Compliant Deposit (FCD) Date

2016-02-04

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