A Membrane-Bound Antiparallel Dimer of Rat Islet Amyloid Polypeptide

Authors


  • This work was funded by an American Heart Association Postdoctoral Fellowship for A.N. and NIH grant GM-084391 to E.R. and A.D.M. We thank Dr. S. G. Sligar (UIUC) for the gift of MSP1D1, Y. Gofman of the Ben-Tal group (Tel Aviv University) for assistance with MCPep, Dr. J. Knight, Dr. T. Craggs, and Dr. C. J. Wilson for critical reading, J. Dunn for expressed IAPP, the W. M. Keck Biotechnology Research Laboratory for peptide synthesis, and the Yale FAS High Performance Computing Center.

Abstract

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Gaining recognition: The structure of a previously unrecognized antiparallel dimer of rat islet amyloid polypeptide bound to anionic membrane nanodiscs was examined by using a combination of single-pair FRET and Rosetta model refinement. Models of the dimer showed a likely interface for lipid binding and suggest key interactions may also occur in the human isoform, thereby providing possible insights into fibril formation in type II diabetes.

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