Conformational preferences of the amylin nucleation site in SDS micelles: An NMR study

Authors

  • Alessandro Mascioni,

    1. Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
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  • Fernando Porcelli,

    1. Department of Environmental Sciences (Di.S.A.) and INFM Sez. B University of Tuscia, Viterbo, Italy
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  • Udayar Ilangovan,

    1. Biophysics Research Division, Department of Chemistry, and Macromolecular Science & Engineering, University of Michigan, Ann Arbor, MI 48109-1055, USA
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  • Ayyalusamy Ramamoorthy,

    Corresponding author
    1. Biophysics Research Division, Department of Chemistry, and Macromolecular Science & Engineering, University of Michigan, Ann Arbor, MI 48109-1055, USA
    • Biophysics Research Division and Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055 USA
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  • Gianluigi Veglia

    Corresponding author
    1. Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
    • Department of Chemistry, University of Minnesota, 139 Smith Hall, 207 Pleasant St. S.E., Minneapolis, MN 55455 USA
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Abstract

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 (hIAPP20–29) 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 hIAPP20–29 in membrane-mimicking environments. We found that upon interacting with negatively charged micelles, the dominant conformation of hIAPP20–29 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

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