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Identification of human plasma C1 inhibitor as a target protein for staphylococcal superantigen-like protein 5 (SSL5)
Authors:Teruaki Oku  Chisato Kurisaka  Yusuke Ando  Tsutomu Tsuji
Affiliation:Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
Abstract:The family of staphylococcal superantigen-like proteins (SSLs) have a structure similar to bacterial superantigens but exhibit no superantigenic activity. These exoproteins have recently been shown to disturb the host immune defense system. One family member, SSL5, was reported to bind to human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and matrix metalloproteinase-9 (MMP-9) and to interfere with leukocyte trafficking. In the present study, we explored human plasma proteins bound by glutathione S-transferase (GST)-tagged recombinant SSL5 (GST-SSL5) and identified plasma protease C1 inhibitor (C1Inh) as a major SSL5-binding protein based on the results of peptide mass fingerprinting analysis with MALDI-TOFMS. GST-SSL5 was found to attenuate the inhibitory activity of recombinant histidine-tagged C1Inh (C1Inh-His) toward complement C1s. We also observed that the treatment of C1Inh-His with neuraminidase markedly decreased its binding to GST-SSL5. Moreover, C1Inh-His produced by Lec2 mutant cells (deficient in sialic acid biosynthesis) showed much lower binding affinity for SSL5 than that produced by the wild-type CHO-K1 cells, as assessed by pull-down assay. These results suggest that SSL5 binds to C1Inh in a sialic acid-dependent fashion and modulates the host immune defense through perturbation of the complement system in association with S. aureus infection.
Keywords:Staphylococcus aureus  SSL5  C1 inhibitor  Complement  Immune perturbation  Sialic acid  SSL  staphylococcal superantigen-like protein  GST  C1Inh  plasma protease C1 inhibitor  MMP-9  matrix metalloproteinase-9  PBS  phosphate-buffered saline  SDS-PAGE  sodium dodecyl sulfate-polyacrylamide gel electrophoresis  MALDI-TOFMS  matrix-assisted laser desorption/ionization-time of flight mass spectrometry  HRP  horseradish peroxidase  DTNB 5  5’-dithiobis(2-nitrobenzoic acid)  PNGase F  Corresponding author.
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