Does the location of a mutation determine the ability to form amyloid fibrils?

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We have previously reported studies of fibril formation by a set of protein G B1 domain (β1) variants, with mutations located around the central parallel β-strands. In this study, we designed multiple mutations in the edge strands of β1 to create proteins with a stability range comparable to that of the set of central mutants. All the edge variants are able to form amyloid fibrils when they are incubated at their melting temperatures. This result suggests that overall protein stability is the key determinant for amyloid formation and not the specific location of destabilizing mutations. The edge strand and variants cross-seed with each other and with members of the central variant family. Interesting fibrillar morphology was observed in some cross-seeding cases and its implications for a better understanding of nucleation and elongation events are discussed.

Original languageEnglish (US)
Pages (from-to)17-22
Number of pages6
JournalJournal of Molecular Biology
Volume323
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Amyloid formation
  • Cross-seeding
  • Protein G B1 domain
  • Protein stability
  • β-sheet

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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