High hydrostatic pressure dissociates early aggregates of TTR105-115, but not the mature amyloid fibrils

C Dirix, F Meersman, C E MacPhee, C M Dobson, K Heremans, Cait MacPhee

Research output: Contribution to journalArticlepeer-review

Abstract

A range of disorders such as Alzheimer's disease and type 11 diabetes have been linked to protein misfolding and aggregation. Transthyretin is an amyloidogenic protein which is involved in familial amyloid polyneuropathy, the most common form of systemic amyloid disease. A peptide fragment of this protein, TTR105-115, has been shown to form well-defined amyloid fibrils in vitro. In this study, the stability of amyloid fibrils towards high hydrostatic pressure has been investigated by Fourier transform infrared spectroscopy Information on the morphology of the species exposed to high hydrostatic pressure was obtained by atomic force microscopy. The species formed early in the aggregation process were found to be dissociated by relatively low hydrostatic pressure (220 MPa), whereas mature fibrils are pressure insensitive up to 1.3 GPa. The pressure stability of the mature fibrils is consistent with a fibril structure in which there is an extensive hydrogen bond network in a tightly packed environment from which water is excluded. The fact that early aggregates can be dissociated by low pressure suggests, however, that hydrophobic and electrostatic interactions are the dominant factors stabilizing the species formed in the early stages of fibril formation. (c) 2005 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalJournal of Molecular Biology
Volume347
Issue number5
DOIs
Publication statusPublished - 15 Apr 2005

Keywords

  • amyloid
  • transthyretin
  • Fourier transform infrared spectroscopy
  • atomic force microscopy
  • hydrogen bonds
  • FTIR SPECTROSCOPY
  • PROTEIN-STRUCTURE
  • ALPHA-SYNUCLEIN
  • FORMING PEPTIDE
  • IN-VITRO
  • TRANSTHYRETIN
  • DYNAMICS
  • REVEALS
  • INSULIN
  • CORE

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