Domain swapping and amyloid fibril conformation

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)

Abstract

For several different proteins an apparent correlation has been observed between the propensity for dimerization by domain-swapping and the ability to aggregate into amyloid-like fibrils. Examples include the disease-related proteins β 2-microglobulin and transthyretin. This has led to proposals that the amyloid-formation pathway may feature extensive domain swapping. One possible consequence of such an aggregation pathway is that the resulting fibrils would incorporate structural elements that resemble the domain-swapped forms of the protein and, thus, reflect certain native-like structures or domain-interactions. In magic angle spinning solid-state NMR-based and other structural studies of such amyloid fibrils, it appears that many of these proteins form fibrils that are not native-like. Several fibrils, instead, have an in-register, parallel conformation, which is a common amyloid structural motif and is seen, for instance, in various prion fibrils. Such a lack of native structure in the fibrils suggests that the apparent connection between domain-swapping ability and amyloid-formation may be more subtle or complex than may be presumed at first glance.
Original languageEnglish
Pages (from-to)211-6
Number of pages6
JournalPrion
Volume6
Issue number3
DOIs
Publication statusPublished - 1-Jul-2012
Externally publishedYes

Keywords

  • Amyloid/chemistry
  • Animals
  • Humans
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Multimerization
  • Protein Structure, Tertiary
  • beta 2-Microglobulin/chemistry
  • HUMAN CYSTATIN-C
  • SOLID-STATE NMR
  • HUMAN PRION PROTEIN
  • ANGLE-SPINNING NMR
  • NATIVE-LIKE
  • BETA-STRANDS
  • CRYSTAL-STRUCTURE
  • TRANSTHYRETIN
  • DIMER
  • BETA-2-MICROGLOBULIN

Fingerprint

Dive into the research topics of 'Domain swapping and amyloid fibril conformation'. Together they form a unique fingerprint.

Cite this