title: Binding Orientations and Lipid Interactions of Human Amylin at Zwitterionic and Anionic Lipid Bilayers.
abstract: 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.
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai 200433, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai 200433, China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
mesh_terms: D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C028694:1-palmitoyl-2-oleoylphosphatidylcholine