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| | <SX load='6nk7' size='340' side='right' viewer='molstar' caption='[[6nk7]], [[Resolution|resolution]] 4.99Å' scene=''> | | <SX load='6nk7' size='340' side='right' viewer='molstar' caption='[[6nk7]], [[Resolution|resolution]] 4.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nk7]] is a 17 chain structure with sequence from [http://en.wikipedia.org/wiki/Chikv Chikv] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NK7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NK7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nk7]] is a 17 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus Chikungunya virus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NK7 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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.99Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIKVgp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37124 CHIKV]), Mxra8, Asp3, Dicam ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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></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=6nk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nk7 OCA], [https://pdbe.org/6nk7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nk7 RCSB], [https://www.ebi.ac.uk/pdbsum/6nk7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nk7 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=6nk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nk7 OCA], [http://pdbe.org/6nk7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nk7 RCSB], [http://www.ebi.ac.uk/pdbsum/6nk7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nk7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MXRA8_MOUSE MXRA8_MOUSE]] Transmembrane protein which can modulate activity of various signaling pathways, probably via binding to integrin ITGAV:ITGB3 (PubMed:18366072, PubMed:22492581, PubMed:29702220). Mediates heterophilic cell-cell interactions in vitro (PubMed:18366072). Inhibits osteoclastogenesis downstream of TNFSF11/RANKL and CSF1, where it may function by attenuating signaling via integrin ITGB3 and MAP kinase p38 (PubMed:22492581). Plays a role in cartilage formation where it promotes proliferation and maturation of growth plate chondrocytes (PubMed:29702220). Stimulates formation of primary cilia in chondrocytes (PubMed:29702220). 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 (PubMed:29702220). Plays a role in angiogenesis where it suppresses migration of endothelial cells and also promotes their apoptosis (By similarity). Inhibits VEGF-induced activation of AKT and p38 MAP kinase in endothelial cells (By similarity). Also inhibits VTN (vitronectin)-mediated integrin ITGAV:ITGB3 signaling and activation of PTK2/FAK (By similarity). May play a role in the maturation and maintenance of the blood-brain barrier (PubMed:14603461).[UniProtKB:Q9BRK3]<ref>PMID:14603461</ref> <ref>PMID:18366072</ref> <ref>PMID:22492581</ref> <ref>PMID:29702220</ref> | + | [https://www.uniprot.org/uniprot/Q88628_CHIKV Q88628_CHIKV] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6nk7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6nk7" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Chikv]] | + | [[Category: Chikungunya virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Togavirin]]
| + | [[Category: Basore K]] |
| - | [[Category: Basore, K]] | + | [[Category: Fremont DH]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Kim AS]] |
| - | [[Category: Fremont, D H]] | + | [[Category: Nelson CA]] |
| - | [[Category: Kim, A S]] | + | |
| - | [[Category: Nelson, C A]] | + | |
| - | [[Category: Chikungunya]]
| + | |
| - | [[Category: Csgid]]
| + | |
| - | [[Category: Mxra8]]
| + | |
| - | [[Category: Viral receptor]]
| + | |
| - | [[Category: Virus]]
| + | |
| Structural highlights
Function
Q88628_CHIKV
Publication Abstract from PubMed
Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 A resolution X-ray crystal structure of Mxra8 and 4 to 5 A resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors.
Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.,Basore K, Kim AS, Nelson CA, Zhang R, Smith BK, Uranga C, Vang L, Cheng M, Gross ML, Smith J, Diamond MS, Fremont DH Cell. 2019 May 6. pii: S0092-8674(19)30392-7. doi: 10.1016/j.cell.2019.04.006. PMID:31080061[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Basore K, Kim AS, Nelson CA, Zhang R, Smith BK, Uranga C, Vang L, Cheng M, Gross ML, Smith J, Diamond MS, Fremont DH. Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor. Cell. 2019 May 6. pii: S0092-8674(19)30392-7. doi: 10.1016/j.cell.2019.04.006. PMID:31080061 doi:http://dx.doi.org/10.1016/j.cell.2019.04.006
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