title: Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels.
abstract: Fundamental understanding of ion channel formation by amyloid peptides, which is strongly linked to cell toxicity, is very critical for (pre)clinical treatment of neurodegenerative diseases. Here, we combine atomistic simulations and experiments to demonstrate a broad range of conformational states of hIAPP double channels in lipid membranes. All individual channels display high selectivity for Cl(-) ions over cations, but the co-existence of polymorphic double channels of different conformations and orientations with different populations determines the non-ionic selectivity nature of the channels, which is different from the typical amyloid-β channels that exhibit Ca(2+) selective ion-permeable characteristics. This work provides a more complete physicochemical mechanism of amyloid-channel-induced toxicity.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325, USA. zhengj@uakron.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Rundong
authors.initials: R
authors.lastname: Hu
authors.forename: Michele F M
authors.initials: MF
authors.lastname: Sciacca
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brender
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000838:Anions / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
chemical_list: D000838:Anions; D002413:Cations, Divalent; D007473:Ion Channels; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D002713:Chlorine; D002118:Calcium