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- W4225571912 abstract "The islet amyloid polypeptide (IAPP) is the main constituent of the amyloid fibrils found in the pancreas of type 2 diabetes patients. The aggregation of IAPP is known to cause cell death, where the cell membrane plays a dual role: being a catalyst of IAPP aggregation and being the target of IAPP toxicity. Using ATR-FTIR spectroscopy, transmission electron microscopy, and molecular dynamics simulations we investigate the very first molecular steps following IAPP binding to a lipid membrane. In particular, we assess the combined effects of the charge state of amino-acid residue 18 and the IAPP-membrane interactions on the structures of monomeric and aggregated IAPP. Distinct IAPP-membrane interaction modes for the various IAPP variants are revealed. Membrane binding causes IAPP to fold into an amphipathic α -helix, which in the case of H18K-, and H18R-IAPP readily moves beyond the headgroup region. For all IAPP variants but H18E-IAPP, the membrane-bound helix is an intermediate on the way to amyloid aggregation, while H18E-IAPP remains in a stable helical conformation. The fibrillar aggregates of wild-type IAPP and H18K-IAPP are dominated by an antiparallel β -sheet conformation, while H18R- and H18A-IAPP exhibit both antiparallel and parallel β -sheets as well as amorphous aggregates. Our results emphasize the decisive role of residue 18 for the structure and membrane interaction of IAPP. This residue is thus a good therapeutic target for destabilizing membrane-bound IAPP fibrils to inhibit their toxic actions." @default.
- W4225571912 created "2022-05-05" @default.
- W4225571912 creator A5011523143 @default.
- W4225571912 creator A5011590056 @default.
- W4225571912 creator A5017415443 @default.
- W4225571912 creator A5054275750 @default.
- W4225571912 creator A5061732933 @default.
- W4225571912 creator A5075480551 @default.
- W4225571912 date "2022-03-15" @default.
- W4225571912 modified "2023-10-10" @default.
- W4225571912 title "Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide" @default.
- W4225571912 cites W1031578623 @default.
- W4225571912 cites W1608388154 @default.
- W4225571912 cites W1966909071 @default.
- W4225571912 cites W1967239474 @default.
- W4225571912 cites W1969553345 @default.
- W4225571912 cites W1970577444 @default.
- W4225571912 cites W1976499671 @default.
- W4225571912 cites W1980233706 @default.
- W4225571912 cites W1984675243 @default.
- W4225571912 cites W1985182189 @default.
- W4225571912 cites W1988583668 @default.
- W4225571912 cites W1990468756 @default.
- W4225571912 cites W1991576961 @default.
- W4225571912 cites W1993811485 @default.
- W4225571912 cites W1994342334 @default.
- W4225571912 cites W1999909300 @default.
- W4225571912 cites W2000893833 @default.
- W4225571912 cites W2001148193 @default.
- W4225571912 cites W2003709444 @default.
- W4225571912 cites W2007839917 @default.
- W4225571912 cites W2008708467 @default.
- W4225571912 cites W2016089333 @default.
- W4225571912 cites W2024849831 @default.
- W4225571912 cites W2030322549 @default.
- W4225571912 cites W2035266068 @default.
- W4225571912 cites W2042036635 @default.
- W4225571912 cites W2050886257 @default.
- W4225571912 cites W2053023958 @default.
- W4225571912 cites W2053402937 @default.
- W4225571912 cites W2056232124 @default.
- W4225571912 cites W2057477511 @default.
- W4225571912 cites W2060878281 @default.
- W4225571912 cites W2061245389 @default.
- W4225571912 cites W2066414494 @default.
- W4225571912 cites W2067820229 @default.
- W4225571912 cites W2068688814 @default.
- W4225571912 cites W2070114315 @default.
- W4225571912 cites W2075784917 @default.
- W4225571912 cites W2080429643 @default.
- W4225571912 cites W2082038580 @default.
- W4225571912 cites W2082186075 @default.
- W4225571912 cites W2097259690 @default.
- W4225571912 cites W2098651156 @default.
- W4225571912 cites W2099280334 @default.
- W4225571912 cites W2100817247 @default.
- W4225571912 cites W2101421775 @default.
- W4225571912 cites W2101995697 @default.
- W4225571912 cites W2108711777 @default.
- W4225571912 cites W2115168896 @default.
- W4225571912 cites W2128460405 @default.
- W4225571912 cites W2131107868 @default.
- W4225571912 cites W2134354670 @default.
- W4225571912 cites W2134909516 @default.
- W4225571912 cites W2136885518 @default.
- W4225571912 cites W2141035467 @default.
- W4225571912 cites W2144481414 @default.
- W4225571912 cites W2145124130 @default.
- W4225571912 cites W2149975011 @default.
- W4225571912 cites W2160497181 @default.
- W4225571912 cites W2160664224 @default.
- W4225571912 cites W2169536198 @default.
- W4225571912 cites W2206954826 @default.
- W4225571912 cites W2265775199 @default.
- W4225571912 cites W2294324796 @default.
- W4225571912 cites W2468038908 @default.
- W4225571912 cites W2555870966 @default.
- W4225571912 cites W2560541065 @default.
- W4225571912 cites W2560560526 @default.
- W4225571912 cites W2570218327 @default.
- W4225571912 cites W2597394997 @default.
- W4225571912 cites W2741661962 @default.
- W4225571912 cites W2749751185 @default.
- W4225571912 cites W2789305939 @default.
- W4225571912 cites W2789514753 @default.
- W4225571912 cites W2791546553 @default.
- W4225571912 cites W2793550642 @default.
- W4225571912 cites W2794387712 @default.
- W4225571912 cites W2969256019 @default.
- W4225571912 cites W3034648294 @default.
- W4225571912 cites W3034727008 @default.
- W4225571912 cites W3048910108 @default.
- W4225571912 cites W3084854026 @default.
- W4225571912 cites W3110343827 @default.
- W4225571912 cites W3111931513 @default.
- W4225571912 cites W3120303451 @default.
- W4225571912 cites W3127602688 @default.
- W4225571912 cites W3152521585 @default.
- W4225571912 cites W3155327875 @default.
- W4225571912 cites W3168207341 @default.