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Neutron diffraction reveals sequence‐specific membrane insertion of pre‐fibrillar islet amyloid polypeptide and inhibition by rifampicin
Author(s) -
Balali-Mood Kia,
Ashley Richard H.,
Hauß Thomas,
Bradshaw Jeremy P.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.12.085
Subject(s) - membrane , biophysics , islet , amyloid (mycology) , chemistry , phospholipid , fibril , peptide , biochemistry , insulin , biology , endocrinology , inorganic chemistry
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.