6nk6
From Proteopedia
(Difference between revisions)
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor== | |
| + | <SX load='6nk6' size='340' side='right' viewer='molstar' caption='[[6nk6]], [[Resolution|resolution]] 4.06Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6nk6]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus_strain_Senegal_37997 Chikungunya virus strain Senegal 37997] 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=6NK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NK6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.06Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nk6 OCA], [https://pdbe.org/6nk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nk6 RCSB], [https://www.ebi.ac.uk/pdbsum/6nk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nk6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:31080061</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6nk6" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: Chikungunya virus strain Senegal 37997]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Basore K]] | ||
| + | [[Category: Fremont DH]] | ||
| + | [[Category: Kim AS]] | ||
| + | [[Category: Nelson CA]] | ||
Current revision
Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor
| |||||||||
