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The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy
journal contribution
posted on 2023-06-09, 00:13 authored by A E Langkilde, K L Morris, Louise SerpellLouise Serpell, D I Svergun, B VestergaardStructural 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.
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Publication status
- Published
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- Published version
Journal
Acta Crystallographica Section D: Biological CrystallographyISSN
1399-0047Publisher
International Union of CrystallographyExternal DOI
Issue
4Volume
71Page range
882-895Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-02-05First Open Access (FOA) Date
2016-02-05First Compliant Deposit (FCD) Date
2016-02-04Usage metrics
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