Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 31, Pages 12837-12841Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202000148
Keywords
amyloids; inhibitors; protein interactions; self-assembly; type 2 diabetes
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Funding
- Deutsche Forschungsgemeinschaft [SFB 1035]
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Amyloid self-assembly of islet amyloid polypeptide (IAPP) is linked to pancreatic inflammation, beta-cell degeneration, and the pathogenesis of type 2 diabetes (T2D). The multifunctional host-defence peptides (HDPs) cathelicidins play crucial roles in inflammation. Here, we show that the antimicrobial and immunomodulatory polypeptide human cathelicidin LL-37 binds IAPP with nanomolar affinity and effectively suppresses its amyloid self-assembly and related pancreatic beta-cell damage in vitro. In addition, we identify key LL-37 segments that mediate its interaction with IAPP. Our results suggest a possible protective role for LL-37 in T2D pathogenesis and offer a molecular basis for the design of LL-37-derived peptides that combine antimicrobial, immunomodulatory, and T2D-related anti-amyloid functions as promising candidates for multifunctional drugs.
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