Actin enables the antimicrobial action of LL-37 peptide in the presence of microbial proteases

Asaf Sol, Yaniv Skvirsky, Rizan Nashef, Katya Zelentsova, Tal Burstyn-Cohen, Edna Blotnick, Andras Muhlrad, Gilad Bachrach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Host defense peptides play an important host-protective role by their microcidal action, immunomodulatory functions, and tissue repair activities. Proteolysis is a common strategy of pathogens used to neutralize host defense peptides. Here, we show that actin, the most abundant structural protein in eukaryotes, binds the LL-37 host defense peptide, protects it from degradation by the proteases of Pseudomonas aeruginosa and Porphyromonas gingivalis, and enables its antimicrobial activity despite the presence of the proteases. Co-localization of LL-37 with extracellular actin was observed in necrotized regions of samples from oral lesions. Competition assays, cross-linking experiments, limited proteolysis, and mass spectrometry revealed that LL-37 binds by specific hydrophobic interactions to the His-40-Lys-50 segment of actin, located in the DNase I binding loop. The integrity of the binding site of both LL-37 and actin is a prerequisite to the binding. Our results demonstrate that actin, presumably released by dead cells and abundant in infected sites, might be utilized by the immune system to enhance spatio-temporal immunity in an attempt to arrest infection and control inflammation.

Original languageAmerican English
Pages (from-to)22926-22941
Number of pages16
JournalJournal of Biological Chemistry
Issue number33
StatePublished - 15 Aug 2014


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