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Conformational preferences of the amylin nucleation site in SDS micelles: An NMR study
Author(s) -
Mascioni Alessandro,
Porcelli Fernando,
Ilangovan Udayar,
Ramamoorthy Ayyalusamy,
Veglia Gianluigi
Publication year - 2003
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10305
Subject(s) - chemistry , amylin , micelle , peptide , amphiphile , amyloid (mycology) , membrane , biophysics , bilayer , nucleation , lipid bilayer , stereochemistry , crystallography , biochemistry , islet , aqueous solution , organic chemistry , copolymer , inorganic chemistry , medicine , insulin , biology , endocrinology , polymer
Human islet amyloid polypeptide (hIAPP), or amylin, is a 37 amino acid hormone secreted by pancreatic β‐cells. hIAPP constitutes ∼90% of the amyloid deposits found in type II diabetic patients. It has been shown that the central region of the peptide (hIAPP 20–29 ) constitutes the nucleation site for the amyloidogenic process with F23 playing a key role in the formation of the β‐pleated structures. In addition, it has been proposed that an important stage in the cytotoxicity of hIAPP is its interaction with the β‐cell membranes. As a first step toward the characterization of the interaction of hIAPP with cell membranes, we determined conformational preferences of hIAPP 20–29 in membrane‐mimicking environments. We found that upon interacting with negatively charged micelles, the dominant conformation of hIAPP 20–29 is a distorted type I β‐turn centered on residues F23 and G24, with F23, A25, and I26 forming a small hydrophobic cluster that may facilitate the interaction of this peptide with the membrane bilayer. Moreover, we were able to elucidate the topological orientation of the peptide that is absorbed on the micelle surface, with the hydrophobic cluster oriented toward the hydrocarbon region of the micelles and both N‐ and C‐termini exposed to the solvent. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 29–41, 2003