Actin Enables the Antimicrobial Action of LL-37 Peptide in the Presence of Microbial Proteases |
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Authors: | Asaf Sol Yaniv Skvirsky Rizan Nashef Katya Zelentsova Tal Burstyn-Cohen Edna Blotnick Andras Muhlrad Gilad Bachrach |
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Institution: | From the ‡Institute of Dental Sciences.;§Department of Oral and Maxillofacial Surgery, Hebrew University-Hadassah School of Dental Medicine and ;the ¶Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Hebrew University of Jerusalem, Jerusalem 91120, Israel |
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Abstract: | 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. |
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Keywords: | Actin Antimicrobial Peptide (AMP) Host Defense Protease Transglutaminase |
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