Neutron diffraction reveals sequence-specific membrane insertion of pre-fibrillar islet amyloid polypeptide and inhibition by rifampicin

Kia Balali-Mood, Richard H. Ashley, Thomas Hauß, Jeremy P. Bradshaw

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Human islet amyloid polypeptide (hIAPP) forms amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). Pre-fibrillar hIAPP oligomers (in contrast to monomeric IAPP or mature fibrils) increase membrane permeability, suggesting an important role in the disease. In the first structural study of membrane-associated hIAPP, lamellar neutron diffraction shows that oligomeric hIAPP inserts into phospholipid bilayers, and extends across the membrane. Rifampicin, which inhibits hIAPP-induced membrane permeabilisation in functional studies, prevents membrane insertion. In contrast, rat IAPP (84% identical to hIAPP, but non-amyloidogenic) does not insert into bilayers. Our findings are consistent with the hypothesis that membrane-active pre-fibrillar hIAPP oligomers insert into beta cell membranes in NIDDM.

Original languageEnglish
Pages (from-to)1143-1148
Number of pages6
JournalFEBS Letters
Volume579
Issue number5
DOIs
Publication statusPublished - 14 Feb 2005

Keywords

  • Alzheimer's disease
  • Diabetes mellitus
  • Ion channel
  • Non-insulin-dependent diabetes mellitus
  • Phospholipid bilayer

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Neutron diffraction reveals sequence-specific membrane insertion of pre-fibrillar islet amyloid polypeptide and inhibition by rifampicin. / Balali-Mood, Kia; Ashley, Richard H.; Hauß, Thomas; Bradshaw, Jeremy P.

In: FEBS Letters, Vol. 579, No. 5, 14.02.2005, p. 1143-1148.

Research output: Contribution to journalArticle

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