title: Resveratrol interferes with the aggregation of membrane-bound human-IAPP: a molecular dynamics study.
abstract: Amyloid aggregation of islet amyloid polypeptide (IAPP) in pancreatic tissues is a typical feature of type 2 diabetes mellitus. Resveratrol, a natural product extensively studied for its wide range of biological effects, has been shown to inhibit IAPP aggregation. However, the mechanism by which resveratrol inhibits IAPP aggregation is still far from complete elucidation. Now, an increasing knowledge of the mechanism of amyloid toxicity shifts the target of research towards the development of compounds which can prevent amyloid-mediated membrane damage rather than merely inhibit fiber formation. In this study we used all atom molecular dynamics to investigate the interaction of resveratrol with full-length human IAPP in a negatively charged membrane environment. Our results show that the presence of resveratrol induces the formation of secondary structures (sheets and helices) by inserting in a hydrophobic pocket between the interaction surface of two IAPP molecules in aqueous solution. On the other hand, resveratrol significantly perturbs the interaction of IAPP with negatively charged membranes by anchoring specific hydrophobic regions (23FGA25 and 32VGS34) of the peptide and forming a stable 1:2 IAPP:resveratrol complex at the water/membrane interphase.
authors: Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania I-95125, Italy; Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.
authors: Fabio
authors: F
authors: Lolicato
authors: Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania I-95125, Italy.
authors: Antonio
authors: A
authors: Raudino
authors: Istituto di Biostrutture e Bioimmagini, CNR, Unità Organizzativa e di Supporto di Catania, Viale A. Doria 6, Catania I-95125, Italy. Electronic address: danilo.milardi@cnr.it.
authors: Danilo
authors: D
authors: Milardi
authors: Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania I-95125, Italy. Electronic address: clarosa@unict.it.
authors: Carmelo
authors: C
authors: La Rosa
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058228:Islet Amyloid Polypeptide; D013267:Stilbenes; D000077185:Resveratrol
keywords: Atomistic simulation; Membrane; Molecular dynamics; Resveratrol; Type II diabetes