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| | <StructureSection load='6jo8' size='340' side='right'caption='[[6jo8]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='6jo8' size='340' side='right'caption='[[6jo8]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jo8]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Chikv Chikv] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JO8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jo8]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus Chikungunya virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JO8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></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]] 3.495Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MXRA8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Togavirin Togavirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.90 3.4.21.90] </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=6jo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jo8 OCA], [https://pdbe.org/6jo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jo8 RCSB], [https://www.ebi.ac.uk/pdbsum/6jo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jo8 ProSAT]</span></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=6jo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jo8 OCA], [http://pdbe.org/6jo8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jo8 RCSB], [http://www.ebi.ac.uk/pdbsum/6jo8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jo8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MXRA8_HUMAN MXRA8_HUMAN]] Transmembrane protein which can modulate activity of various signaling pathways, probably via binding to integrin ITGAV:ITGB3 (PubMed:22492581, PubMed:23386276). Mediates heterophilic cell-cell interactions in vitro (By similarity). Inhibits osteoclastogenesis downstream of TNFSF11/RANKL and CSF1, where it may function by attenuating signaling via integrin ITGB3 and MAP kinase p38 (By similarity). Plays a role in cartilage formation where it promotes proliferation and maturation of growth plate chondrocytes (By similarity). Stimulates formation of primary cilia in chondrocytes (By similarity). Enhances expression of genes involved in the hedgehog signaling pathway in chondrocytes, including the hedgehog signaling molecule IHH; may also promote signaling via the PTHLH/PTHrP pathway (By similarity). Plays a role in angiogenesis where it suppresses migration of endothelial cells and also promotes their apoptosis (PubMed:23386276). Inhibits VEGF-induced activation of AKT and p38 MAP kinase in endothelial cells (PubMed:23386276). Also inhibits VTN (vitronectin)-mediated integrin ITGAV:ITGB3 signaling and activation of PTK2/FAK (PubMed:23386276). May play a role in the maturation and maintenance of the blood-brain barrier (By similarity).[UniProtKB:Q9DBV4]<ref>PMID:22492581</ref> <ref>PMID:23386276</ref> (Microbial infection) Contributes to arthritogenic alphavirus pathogenesis and acts as a receptor for these viruses.<ref>PMID:29769725</ref> | + | [https://www.uniprot.org/uniprot/C8YZ73_CHIKV C8YZ73_CHIKV] |
| | <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: Chikv]] | |
| - | [[Category: Human]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Togavirin]] | |
| - | [[Category: Gao, F]] | |
| - | [[Category: Gao, F G]] | |
| - | [[Category: Qi, J]] | |
| - | [[Category: Song, H]] | |
| - | [[Category: Zhao, Z]] | |
| - | [[Category: Arthritogenic alphaviruse]] | |
| | [[Category: Chikungunya virus]] | | [[Category: Chikungunya virus]] |
| - | [[Category: Mxra8]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Receptor]] | + | [[Category: Large Structures]] |
| - | [[Category: Viral protein]] | + | [[Category: Gao F]] |
| | + | [[Category: Gao FG]] |
| | + | [[Category: Qi J]] |
| | + | [[Category: Song H]] |
| | + | [[Category: Zhao Z]] |
| Structural highlights
Function
C8YZ73_CHIKV
Publication Abstract from PubMed
Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), cause severe and debilitating rheumatic diseases worldwide, resulting in severe morbidity and economic costs. Recently, MXRA8 was reported as an entry receptor. Here, we present the crystal structures of the mouse MXRA8, human MXRA8 in complex with the CHIKV E protein, and the cryo-electron microscopy structure of human MXRA8 and CHIKV virus-like particle. MXRA8 has two Ig-like domains with unique structural topologies. This receptor binds in the "canyon" between two protomers of the E spike on the surface of the virion. The atomic details at the interface between the two binding entities reveal that both the two domains and the hinge region of MXRA8 are involved in interaction with CHIKV E1-E2 residues from two protomers. Notably, the stalk region of MXRA8 is critical for CHIKV virus entry. This finding provides important information regarding the development of therapeutic countermeasures against those arthritogenic alphaviruses.
Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein.,Song H, Zhao Z, Chai Y, Jin X, Li C, Yuan F, Liu S, Gao Z, Wang H, Song J, Vazquez L, Zhang Y, Tan S, Morel CM, Yan J, Shi Y, Qi J, Gao F, Gao GF Cell. 2019 Jun 13;177(7):1714-1724.e12. doi: 10.1016/j.cell.2019.04.008. Epub, 2019 May 9. PMID:31080063[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Song H, Zhao Z, Chai Y, Jin X, Li C, Yuan F, Liu S, Gao Z, Wang H, Song J, Vazquez L, Zhang Y, Tan S, Morel CM, Yan J, Shi Y, Qi J, Gao F, Gao GF. Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein. Cell. 2019 Jun 13;177(7):1714-1724.e12. doi: 10.1016/j.cell.2019.04.008. Epub, 2019 May 9. PMID:31080063 doi:http://dx.doi.org/10.1016/j.cell.2019.04.008
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