The Human Host-Defense Peptide Cathelicidin LL-37 is a Nanomolar Inhibitor of Amyloid Self-Assembly of Islet Amyloid Polypeptide (IAPP).
Angew Chem Int Ed Engl
; 59(31): 12837-12841, 2020 07 27.
Article
em En
| MEDLINE
| ID: mdl-31999880
ABSTRACT
Amyloid self-assembly of islet amyloid polypeptide (IAPP) is linked to pancreatic inflammation, ß-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 ß-cell damage inâ
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Catiônicos Antimicrobianos
/
Multimerização Proteica
/
Polipeptídeo Amiloide das Ilhotas Pancreáticas
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha