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| | ==Crystal Structure of the PDZ domain of RhoGEF bound to CXCR2 C-terminal peptide== | | ==Crystal Structure of the PDZ domain of RhoGEF bound to CXCR2 C-terminal peptide== |
| - | <StructureSection load='5tyt' size='340' side='right' caption='[[5tyt]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5tyt' size='340' side='right'caption='[[5tyt]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tyt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TYT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TYT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tyt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TYT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CXCR2, IL8RB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.398Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tyt OCA], [http://pdbe.org/5tyt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tyt RCSB], [http://www.ebi.ac.uk/pdbsum/5tyt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tyt 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=5tyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tyt OCA], [https://pdbe.org/5tyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tyt RCSB], [https://www.ebi.ac.uk/pdbsum/5tyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tyt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ARHGB_HUMAN ARHGB_HUMAN]] May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. | + | [https://www.uniprot.org/uniprot/ARHGB_HUMAN ARHGB_HUMAN] May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Brunzelle, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Choudhary, V]] | + | [[Category: Brunzelle J]] |
| - | [[Category: Holcomb, J]] | + | [[Category: Choudhary V]] |
| - | [[Category: Li, C]] | + | [[Category: Holcomb J]] |
| - | [[Category: Niu, A]] | + | [[Category: Li C]] |
| - | [[Category: Spellmon, N]] | + | [[Category: Niu A]] |
| - | [[Category: Sun, X]] | + | [[Category: Spellmon N]] |
| - | [[Category: Yang, Z]] | + | [[Category: Sun X]] |
| - | [[Category: Cxcr2]]
| + | [[Category: Yang Z]] |
| - | [[Category: Pdz-rhogef]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
ARHGB_HUMAN May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.
Publication Abstract from PubMed
The CXC chemokine receptor 2 (CXCR2) is a G protein coupled receptor mediating interleukin-8 chemotactic signaling and plays an important role in neutrophil mobility and tumor migration. However, efficient CXCR2 signaling requires PDZ domain-mediated scaffolding of signaling complexes at the plasma membrane and functional coupling of the signaling to specific downstream signaling pathways, in which only one PDZ protein has been characterized to interact with CXCR2. Here, we identified five novel CXCR2-binding PDZ-containing proteins, among which PDZ-RhoGEF is of particular interest because this PDZ and RGS-containing guanine nucleotide exchange factor (GEF) is also involved in cell signaling and mobility. To reveal the molecular basis of the interaction, we solved the crystal structure of PDZ-RhoGEF PDZ domain in complex with the CXCR2 C-terminal PDZ binding motif. The structure reveals that the PDZ-CXCR2 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four CXCR2 residues contributing to specific interactions. Structural comparison of CXCR2-binding PDZ domains and PDZ-RhoGEF PDZ bound with different ligands reveals PDZ- and ligand-specific interactions that may underlie the ability of promiscuous CXCR2 binding by different PDZ domains and PDZ binding promiscuity. The structure also reveals an unexpected asymmetric disulfide bond-linked PDZ dimer that allows simultaneous parallel binding of CXCR2 to two PDZ domains. This study provides not only the structural basis for PDZ-mediated CXCR2-PDZ-RhoGEF interaction, but also a new mode of PDZ dimerization, which both could prove valuable in understanding signaling complex scaffolding in CXCR2 signaling and coupling to specific signaling pathways.
Structural basis of PDZ-mediated chemokine receptor CXCR2 scaffolding by guanine nucleotide exchange factor PDZ-RhoGEF.,Spellmon N, Holcomb J, Niu A, Choudhary V, Sun X, Zhang Y, Wan J, Doughan M, Hayden S, Hachem F, Brunzelle J, Li C, Yang Z Biochem Biophys Res Commun. 2017 Apr 1;485(2):529-534. doi:, 10.1016/j.bbrc.2017.02.010. Epub 2017 Feb 6. PMID:28179147[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Spellmon N, Holcomb J, Niu A, Choudhary V, Sun X, Zhang Y, Wan J, Doughan M, Hayden S, Hachem F, Brunzelle J, Li C, Yang Z. Structural basis of PDZ-mediated chemokine receptor CXCR2 scaffolding by guanine nucleotide exchange factor PDZ-RhoGEF. Biochem Biophys Res Commun. 2017 Apr 1;485(2):529-534. doi:, 10.1016/j.bbrc.2017.02.010. Epub 2017 Feb 6. PMID:28179147 doi:http://dx.doi.org/10.1016/j.bbrc.2017.02.010
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