Neutron diffraction reveals sequence‐specific membrane insertion of pre‐fibrillar islet amyloid polypeptide and inhibition by rifampicin
- 19 January 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (5) , 1143-1148
- https://doi.org/10.1016/j.febslet.2004.12.085
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 NIDDMKeywords
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