TY - JOUR A2 - Khemtemourian, Lucie AU - Qian, Zhenyu AU - Jia, Yan AU - Wei, Guanghong PY - 2016 DA - 2015/11/16 TI - Binding Orientations and Lipid Interactions of Human Amylin at Zwitterionic and Anionic Lipid Bilayers SP - 1749196 VL - 2016 AB - Increasing evidence suggests that the interaction of human islet amyloid polypeptide (hIAPP) with lipids may facilitate hIAPP aggregation and cause the death of pancreatic islet β-cells. However, the detailed hIAPP-membrane interactions and the influences of lipid compositions are unclear. In this study, as a first step to understand the mechanism of membrane-mediated hIAPP aggregation, we investigate the binding behaviors of hIAPP monomer at zwitterionic palmitoyloleoyl-phosphatidylcholine (POPC) bilayer by performing atomistic molecular dynamics simulations. The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers. We find that the adsorption of hIAPP to POPC bilayer is mainly initiated from the C-terminal region and the peptide adopts a helical structure with multiple binding orientations, while the adsorption to POPG bilayer is mostly initiated from the N-terminal region and hIAPP displays one preferential binding orientation, with its hydrophobic residues exposed to water. hIAPP monomer inserts into POPC lipid bilayers more readily than into POPG bilayers. Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids. This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers. SN - 2314-6745 UR - https://doi.org/10.1155/2016/1749196 DO - 10.1155/2016/1749196 JF - Journal of Diabetes Research PB - Hindawi Publishing Corporation KW - ER -