title: Actin enables the antimicrobial action of LL-37 peptide in the presence of microbial proteases.
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.
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Sol
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Skvirsky
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hebrew University-Hadassah School of Dental Medicine and Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Rizan
authors.initials: R
authors.lastname: Nashef
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Katya
authors.initials: K
authors.lastname: Zelentsova
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Burstyn-Cohen
authors.affiliation: Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Edna
authors.initials: E
authors.lastname: Blotnick
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Andras
authors.initials: A
authors.lastname: Muhlrad
authors.affiliation: Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: giladba@ekmd.huji.ac.il.
authors.forename: Gilad
authors.initials: G
authors.lastname: Bachrach
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D016866:Bacteroidaceae Infections / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D017433:Protein Structure, Secondary; D059748:Proteolysis; D011552:Pseudomonas Infections / Q000378:metabolism / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D054804:Cathelicidins
chemical_list: D000199:Actins; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D010447:Peptide Hydrolases; D054804:Cathelicidins
keywords: Actin; Antimicrobial Peptide (AMP); Host Defense; Protease; Transglutaminase