Formation of receptor-independent channels by hIAPP in the membrane is regarded as one of the membrane-damaging mechanisms associated with the dysfunction and death of pancreatic islet �-cells in type II diabetes. Here, we investigate dynamic structure, ion conductivity, and membrane interactions of hIAPP channels in the DOPC bilayer using molecular dynamics simulations. In the simulated lipid environments, a series of annular-like hIAPP structures with different sizes and topologies are compatible with the doughnut-like images obtained by AFM, and with those of modeled channels for A�, K3 peptide, and antimicrobial peptide PG-1, suggesting that loosely-associated �-structure motifs can be a general feature of toxic, unregulated channels. All channels induce directional permeability of multiple ions across the bilayers. This study represents a first attempt to delineate some of the main structural features of the hIAPP channels, for a better understanding of the origin of amyloid toxicity and the development of pharmaceutical agents.

Investigating ion channel activity of human islet amyloid polypeptide (amylin) using molecular dynamics simulations

245th National Meeting (2013)

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