Research article summary (published 25 Aug 2009):

Chemokine degradation by the Group A streptococcal serine proteinase ScpC can be reconstituted in vitro and requires two separate domains.

Full Abstract

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.

Author information

Author/s: Fritzer, Andrea (A); Noiges, Birgit (B); Schweiger, Daniela (D); Rek, Angelika (A); Kungl, Andreas J (AJ); von Gabain, Alexander (A); Nagy, Eszter (E); Meinke, Andreas L (AL);

Affiliation: Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Biochemical journal (Biochem J), published in England. (Language: eng)

Reference: 2009-Sep; vol 422 (issue 3) : pp 533-42

Dates: Created 2009/08/24; Completed 2009/09/16;

PMID: 19552626, status: MEDLINE (last retrieval date: 9/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Bacterial Proteins - genetics; metabolism Chemokines - metabolism Chemokines, CXC - metabolism Immunoblotting Interleukin-8 - metabolism Protein Binding

Protein Structure, Tertiary Recombinant Proteins - genetics; metabolism Serine Endopeptidases - genetics; metabolism Streptococcus pyogenes - enzymology; genetics Substrate Specificity Surface Plasmon Resonance

Associated Chemicals: Bacterial Proteins (0) ; Chemokines (0) ; Chemokines, CXC (0) ; Interleukin-8 (0) ; Recombinant Proteins (0) ; Serine Endopeptidases (EC 3.4.21.-)

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