Chemokine degradation by the Group A streptococcal serine proteinase ScpC can be reconstituted in vitro and requires two separate domains
| Autor: | Eszter Nagy, Andreas Meinke, Angelika Rek, Birgit Noiges, Alexander von Gabain, Daniela Schweiger, Andreas J. Kungl, Andrea Fritzer |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Chemokine
Streptococcus pyogenes medicine.medical_treatment Immunoblotting medicine.disease_cause Biochemistry Substrate Specificity Serine 03 medical and health sciences Bacterial Proteins medicine CXC chemokine receptors Molecular Biology 030304 developmental biology 0303 health sciences Protease biology 030306 microbiology Interleukin-8 Serine Endopeptidases Cell Biology Surface Plasmon Resonance Recombinant Proteins Protein Structure Tertiary 3. Good health Cell biology CXCL2 biology.protein CXCL9 Chemokines Chemokines CXC Platelet factor 4 Protein Binding |
| Zdroj: | Biochemical Journal. 422:533-542 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20090278 |
| Popis: | Streptococcus pyogenes is one of the most common human pathogens and possesses diverse mechanisms to evade the human immune defence. One example of its immune evasion is the degradation of the chemokine IL (interleukin)-8 by ScpC, a serine proteinase that prevents the recruitment of neutrophils to an infection site. By applying the ANTIGENome technology and using human serum antibodies, we identified Spy0416, annotated as ScpC, as a prominent antigen that induces protective immune responses in animals. We demonstrate here for the first time that the recombinant form of Spy0416 is capable of IL-8 degradation in vitro in a concentration- and time-dependent manner. Mutations in the conserved amino acid residues of the catalytic triad of Spy0416 completely abolished in vitro activity. However, the isolated predicted proteinase domain does not exhibit IL-8-degrading activity, but is dependent on the presence of the C-terminal region of Spy0416. Binding to IL-8 is mainly mediated by the catalytic domain. However, the C-terminal region modulates substrate binding, indicating that the proteolytic activity is amenable to regulation via the non-catalytic regions. The specificity for human substrates is not restricted to IL-8, since we also detected in vitro protease activity for another CXC chemokine GRO-alpha (growth-related oncogene alpha), but not for NAP-2 (neutrophil-activating protein 2), SDF (stromal-cell-derived factor)-1alpha, PF-4 (platelet factor 4), I-TAC (interferon-gamma-inducible T-cell alpha-chemoattractant), IP-10 (interferon-gamma-inducible protein 10) and MCP-1 (monocyte chemoattractant protein 1). The degradation of two human CXC chemokines in vitro, the high sequence conservation, the immunogenicity of the protein in humans and the shown protection in animal studies suggest that Spy0416 is a promising vaccine candidate for the prevention of infections by S. pyogenes. |
| Databáze: | OpenAIRE |
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