|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the tyrosine-sulfated C5a receptor N-terminus in complex with the immune evasion protein CHIPS.== | | ==Structure of the tyrosine-sulfated C5a receptor N-terminus in complex with the immune evasion protein CHIPS.== |
| - | <StructureSection load='2k3u' size='340' side='right'caption='[[2k3u]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | + | <StructureSection load='2k3u' size='340' side='right'caption='[[2k3u]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k3u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staae Staae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K3U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k3u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_str._Newman Staphylococcus aureus subsp. aureus str. Newman]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K3U FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xee|1xee]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">chp, NWMN_1877 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=426430 STAAE])</td></tr> | + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k3u OCA], [https://pdbe.org/2k3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k3u RCSB], [https://www.ebi.ac.uk/pdbsum/2k3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k3u ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k3u OCA], [https://pdbe.org/2k3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k3u RCSB], [https://www.ebi.ac.uk/pdbsum/2k3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k3u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CHIPS_STAAE 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.<ref>PMID:14993252</ref> <ref>PMID:15153520</ref>
| + | [https://www.uniprot.org/uniprot/CHIPS_STAAE 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.<ref>PMID:14993252</ref> <ref>PMID:15153520</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 24: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Staae]] | + | [[Category: Staphylococcus aureus subsp. aureus str. Newman]] |
| - | [[Category: Bunschoten, A]] | + | [[Category: Bunschoten A]] |
| - | [[Category: Ippel, J H]] | + | [[Category: Ippel JH]] |
| - | [[Category: Kemmink, J]] | + | [[Category: Kemmink J]] |
| - | [[Category: Liskamp, R]] | + | [[Category: Liskamp R]] |
| - | [[Category: Anaphylotoxin c5a]]
| + | |
| - | [[Category: Complement cascade]]
| + | |
| - | [[Category: Gpcr membrane protein c5ar]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Staphylococcus aureus]]
| + | |
| - | [[Category: Sulfated tyrosine]]
| + | |
| - | [[Category: Virulence]]
| + | |
| 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
Complement component C5a is a potent pro-inflammatory agent inducing chemotaxis of leukocytes toward sites of infection and injury. C5a mediates its effects via its G protein-coupled C5a receptor (C5aR). Although under normal conditions highly beneficial, excessive levels of C5a can be deleterious to the host and have been related to numerous inflammatory diseases. A natural inhibitor of the C5aR is chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). CHIPS is a 121-residue protein excreted by S. aureus. It binds the N terminus of the C5aR (residues 1-35) with nanomolar affinity and thereby potently inhibits C5a-mediated responses in human leukocytes. Therefore, CHIPS provides a starting point for the development of new anti-inflammatory agents. Two O-sulfated tyrosine residues located at positions 11 and 14 within the C5aR N terminus play a critical role in recognition of C5a, but their role in CHIPS binding has not been established so far. By isothermal titration calorimetry, using synthetic Tyr-11- and Tyr-14-sulfated and non-sulfated C5aR N-terminal peptides, we demonstrate that the sulfate groups are essential for tight binding between the C5aR and CHIPS. In addition, the NMR structure of the complex of CHIPS and a sulfated C5aR N-terminal peptide reveals the precise binding motif as well as the distinct roles of sulfated tyrosine residues sY11 and sY14. These results provide a molecular framework for the design of novel CHIPS-based C5aR inhibitors.
Structure of the tyrosine-sulfated C5a receptor N terminus in complex with chemotaxis inhibitory protein of Staphylococcus aureus.,Ippel JH, de Haas CJ, Bunschoten A, van Strijp JA, Kruijtzer JA, Liskamp RM, Kemmink J J Biol Chem. 2009 May 1;284(18):12363-72. Epub 2009 Feb 27. PMID:19251703[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
- ↑ Ippel JH, de Haas CJ, Bunschoten A, van Strijp JA, Kruijtzer JA, Liskamp RM, Kemmink J. Structure of the tyrosine-sulfated C5a receptor N terminus in complex with chemotaxis inhibitory protein of Staphylococcus aureus. J Biol Chem. 2009 May 1;284(18):12363-72. Epub 2009 Feb 27. PMID:19251703 doi:10.1074/jbc.M808179200
|
