| Structural highlights
Function
[CHIPS_STAAE] Involved in countering the first line of host defense mechanisms. Specifically inhibits the response of human neutrophils and monocytes to complement anaphylatoxin C5a and formylated peptides, like N-formyl-methionyl-leucyl-phenylalanine (fMLP). Acts by binding directly to the C5a receptor (C5aR) and formylated peptide receptor (FPR), thereby blocking the C5a- and fMLP-induced calcium responses. Prevents phagocytosis of the bacterium.[1] [2]
Publication Abstract from PubMed
The chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is a 121 residue excreted virulence factor. It acts by binding the C5a- (C5aR) and formylated peptide receptor (FPR) and thereby blocks specific phagocyte responses. Here, we report the solution structure of a CHIPS fragment consisting of residues 31-121 (CHIPS31-121). CHIPS31-121 has the same activity in blocking the C5aR compared to full-length CHIPS, but completely lacks FPR antagonism. CHIPS31-121 has a compact fold comprising an alpha-helix (residues 38-51) packed onto a four-stranded anti-parallel beta-sheet. Strands beta2 and beta3 are joined by a long loop with a relatively well-defined conformation. Comparison of CHIPS31-121 with known structures reveals striking homology with the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, and the staphyloccocal and streptococcal superantigens TSST-1 and SPE-C. Also, the recently reported structures of several domains of the staphylococcal extracellullar adherence protein (EAP) show a high degree of structural similarity with CHIPS. Most of the conserved residues in CHIPS and its structural homologues are present in the alpha-helix. A conserved arginine residue (R46 in CHIPS) appears to be involved in preservation of the structure. Site-directed mutagenesis of all positively charged residues in CHIPS31-121 reveals a major involvement of arginine 44 and lysine 95 in C5aR antagonism. The structure of CHIPS31-121 will be vital in the further unraveling of its precise mechanism of action. Its structural homology to S.aureus SSLs, superantigens, and EAP might help the design of future experiments towards an understanding of the relationship between structure and function of these proteins.
The structure of the C5a receptor-blocking domain of chemotaxis inhibitory protein of Staphylococcus aureus is related to a group of immune evasive molecules.,Haas PJ, de Haas CJ, Poppelier MJ, van Kessel KP, van Strijp JA, Dijkstra K, Scheek RM, Fan H, Kruijtzer JA, Liskamp RM, Kemmink J J Mol Biol. 2005 Nov 4;353(4):859-72. Epub 2005 Sep 23. PMID:16213522[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Haas CJ, Veldkamp KE, Peschel A, Weerkamp F, Van Wamel WJ, Heezius EC, Poppelier MJ, Van Kessel KP, van Strijp JA. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med. 2004 Mar 1;199(5):687-95. PMID:14993252 doi:http://dx.doi.org/10.1084/jem.20031636
- ↑ Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ, van Kessel KP. Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol. 2004 Jun 1;172(11):6994-7001. PMID:15153520
- ↑ Haas PJ, de Haas CJ, Poppelier MJ, van Kessel KP, van Strijp JA, Dijkstra K, Scheek RM, Fan H, Kruijtzer JA, Liskamp RM, Kemmink J. The structure of the C5a receptor-blocking domain of chemotaxis inhibitory protein of Staphylococcus aureus is related to a group of immune evasive molecules. J Mol Biol. 2005 Nov 4;353(4):859-72. Epub 2005 Sep 23. PMID:16213522 doi:S0022-2836(05)01067-3
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