TY - JOUR
T1 - Actin enables the antimicrobial action of LL-37 peptide in the presence of microbial proteases
AU - Sol, Asaf
AU - Skvirsky, Yaniv
AU - Nashef, Rizan
AU - Zelentsova, Katya
AU - Burstyn-Cohen, Tal
AU - Blotnick, Edna
AU - Muhlrad, Andras
AU - Bachrach, Gilad
PY - 2014/8/15
Y1 - 2014/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84905989203&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.579672
DO - 10.1074/jbc.M114.579672
M3 - Article
C2 - 24947511
AN - SCOPUS:84905989203
SN - 0021-9258
VL - 289
SP - 22926
EP - 22941
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 33
ER -