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 MAPP, 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 MAPP oligomers insert into beta cell membranes in NIDDM. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Original language | English |
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Pages (from-to) | 1143-1148 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 579 |
Issue number | 5 |
DOIs | |
Publication status | Published - 14 Feb 2005 |
Keywords
- Alzheimer's disease
- diabetes mellitus
- ion channel
- non-insulin-dependent diabetes mellitus
- phospholipid bilayer
- SALMON-CALCITONIN
- PROTEINS
- CONFORMATIONS
- LIPOSOMES
- MECHANISM
- TOXICITY
- CHANNEL