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

Valentina Armiento, Kathleen Hille, Denise Naltsas, Jennifer S. Lin, Annelise E. Barron, Aphrodite Kapurniotu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)12837-12841
Number of pages5
JournalAngewandte Chemie International Edition in English
Volume59
Issue number31
DOIs
StatePublished - 27 Jul 2020

Keywords

  • amyloids
  • inhibitors
  • protein interactions
  • self-assembly
  • type 2 diabetes

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