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| | <StructureSection load='6e47' size='340' side='right'caption='[[6e47]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='6e47' size='340' side='right'caption='[[6e47]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6e47]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E47 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6e47]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1] 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=6E47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E47 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHO:GLYCOCHENODEOXYCHOLIC+ACID'>CHO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lq6|3lq6]], [[6e48|6e48]], [[6c6q|6c6q]], [[6c74|6c74]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHO:GLYCOCHENODEOXYCHOLIC+ACID'>CHO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD300lf, CLM1, DIR2, IREM1, LMIR3, PIGR3, IgSF13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6e47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e47 OCA], [https://pdbe.org/6e47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e47 RCSB], [https://www.ebi.ac.uk/pdbsum/6e47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e47 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=6e47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e47 OCA], [http://pdbe.org/6e47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e47 RCSB], [http://www.ebi.ac.uk/pdbsum/6e47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e47 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLM1_MOUSE CLM1_MOUSE]] Acts as an inhibitory receptor for myeloid cells and mast cells. Inhibits osteoclast formation. Induces macrophage cell death upon engagement.<ref>PMID:14662855</ref> <ref>PMID:17438331</ref> <ref>PMID:18097021</ref> | + | [https://www.uniprot.org/uniprot/CAPSD_MNV1 CAPSD_MNV1] Capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry, about 38 nm in diameter, and consisting of 180 capsid proteins. A smaller form of capsid with a diameter of 23 nm might be capsid proteins assembled as icosahedron with T=1 symmetry. The capsid encapsulates the genomic RNA and is decorated with VP2 proteins (By similarity). Mediates virion attachment to the host cell receptor CD300LF (PubMed:27540007, PubMed:30194229).[UniProtKB:Q83884]<ref>PMID:27540007</ref> <ref>PMID:30194229</ref> |
| | <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 6e47" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6e47" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | |
| | [[Category: Murine norovirus 1]] | | [[Category: Murine norovirus 1]] |
| - | [[Category: Fremont, D H]] | + | [[Category: Mus musculus]] |
| - | [[Category: Nelson, C A]] | + | [[Category: Fremont DH]] |
| - | [[Category: Bile acid]] | + | [[Category: Nelson CA]] |
| - | [[Category: Capsid protein]]
| + | |
| - | [[Category: Clm-1]]
| + | |
| - | [[Category: Clm1]]
| + | |
| - | [[Category: Cmrf-35-like molecule-1]]
| + | |
| - | [[Category: Dir2]]
| + | |
| - | [[Category: Gcdca]]
| + | |
| - | [[Category: Igsf13]]
| + | |
| - | [[Category: Irem1]]
| + | |
| - | [[Category: Lmir3]]
| + | |
| - | [[Category: Myeloid receptor]]
| + | |
| - | [[Category: Norovirus]]
| + | |
| - | [[Category: Pigr3]]
| + | |
| - | [[Category: Protruding domain]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
CAPSD_MNV1 Capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry, about 38 nm in diameter, and consisting of 180 capsid proteins. A smaller form of capsid with a diameter of 23 nm might be capsid proteins assembled as icosahedron with T=1 symmetry. The capsid encapsulates the genomic RNA and is decorated with VP2 proteins (By similarity). Mediates virion attachment to the host cell receptor CD300LF (PubMed:27540007, PubMed:30194229).[UniProtKB:Q83884][1] [2]
Publication Abstract from PubMed
Murine norovirus (MNoV) is closely related to human norovirus (HNoV), an infectious agent responsible for acute gastroenteritis worldwide. Here we report the X-ray crystal structure of the dimeric MNoV VP1 protruding (P) domain in complex with its cellular receptor CD300lf. CD300lf binds the P domain with a 2:2 stoichiometry, engaging a cleft between the AB and DE loops of the P2 subdomain at a site that overlaps the epitopes of neutralizing antibodies. We also identify that bile acids are cofactors enhancing MNoV cell-binding and infectivity. Structures of CD300lf-P domain in complex with glycochenodeoxycholic acid (GCDCA) and lithocholic acid (LCA) reveal two bile acid binding sites at the P domain dimer interface distant from receptor binding sites. The structural determinants for receptor and bile acid binding are supported by numerous biophysical assays utilizing interface residue mutations. We find that the monomeric affinity of CD300lf for the P domain is low and is divalent cation dependent. We have also determined the crystal structure of CD300lf in complex with phosphocholine, revealing that MNoV engages its receptor in a manner mimicking host ligands including similar metal coordination. Docking of the cocomplex structures onto a cryo-EM-derived model of MNoV suggests that each virion can make multiple CD300lf engagements, and thus, infection may be driven by the avidity of cell surface clustered CD300lf. These studies identify multiple potential modulators of norovirus infection that may act to regulate the interaction between the viral capsid P domain and its cognate cellular receptor.
Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor.,Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH Proc Natl Acad Sci U S A. 2018 Sep 7. pii: 1805797115. doi:, 10.1073/pnas.1805797115. PMID:30194229[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science. 2016 Aug 26;353(6302):933-6. doi: 10.1126/science.aaf1220. Epub 2016 Aug, 18. PMID:27540007 doi:http://dx.doi.org/10.1126/science.aaf1220
- ↑ Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proc Natl Acad Sci U S A. 2018 Sep 7. pii: 1805797115. doi:, 10.1073/pnas.1805797115. PMID:30194229 doi:http://dx.doi.org/10.1073/pnas.1805797115
- ↑ Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proc Natl Acad Sci U S A. 2018 Sep 7. pii: 1805797115. doi:, 10.1073/pnas.1805797115. PMID:30194229 doi:http://dx.doi.org/10.1073/pnas.1805797115
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