The Human Host-Defense Peptide Cathelicidin LL-37 is a Nanomolar Inhibitor of Amyloid Self-Assembly of Islet Amyloid Polypeptide (IAPP).

ABSTRACT: Amyloid self-assembly of islet amyloid polypeptide (IAPP) is linked to pancreatic inflammation, ?-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 ?-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.

SUBMITTER: Armiento V 

PROVIDER: S-EPMC7497016 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature