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| | <StructureSection load='6oil' size='340' side='right'caption='[[6oil]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6oil' size='340' side='right'caption='[[6oil]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6oil]] is a 1 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=6OIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OIL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6oil]] is a 1 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=6OIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OIL 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">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VSIR ([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></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=6oil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oil OCA], [http://pdbe.org/6oil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oil RCSB], [http://www.ebi.ac.uk/pdbsum/6oil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oil 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=6oil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oil OCA], [https://pdbe.org/6oil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oil RCSB], [https://www.ebi.ac.uk/pdbsum/6oil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oil ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VISTA_HUMAN VISTA_HUMAN]] Immunoregulatory receptor which inhibits the T-cell response (PubMed:24691993). May promote differentiation of embryonic stem cells, by inhibiting BMP4 signaling (By similarity). May stimulate MMP14-mediated MMP2 activation (PubMed:20666777).[UniProtKB:Q9D659]<ref>PMID:20666777</ref> <ref>PMID:24691993</ref> | + | [https://www.uniprot.org/uniprot/VISTA_HUMAN VISTA_HUMAN] Immunoregulatory receptor which inhibits the T-cell response (PubMed:24691993). May promote differentiation of embryonic stem cells, by inhibiting BMP4 signaling (By similarity). May stimulate MMP14-mediated MMP2 activation (PubMed:20666777).[UniProtKB:Q9D659]<ref>PMID:20666777</ref> <ref>PMID:24691993</ref> |
| | <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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cochran, J R]] | + | [[Category: Cochran JR]] |
| - | [[Category: Mathews, I I]] | + | [[Category: Mathews II]] |
| - | [[Category: Mehta, N]] | + | [[Category: Mehta N]] |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Suppressor]]
| + | |
| - | [[Category: T cell activation]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
VISTA_HUMAN Immunoregulatory receptor which inhibits the T-cell response (PubMed:24691993). May promote differentiation of embryonic stem cells, by inhibiting BMP4 signaling (By similarity). May stimulate MMP14-mediated MMP2 activation (PubMed:20666777).[UniProtKB:Q9D659][1] [2]
Publication Abstract from PubMed
V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint protein that inhibits the T cell response against cancer. Similar to PD-1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Here, we report a 1.85 A crystal structure of the elusive human VISTA extracellular domain, whose lack of homology necessitated a combinatorial MR-Rosetta approach for structure determination. We highlight features that make the VISTA immunoglobulin variable (IgV)-like fold unique among B7 family members, including two additional disulfide bonds and an extended loop region with an attached helix that we show forms a contiguous binding epitope for a clinically relevant anti-VISTA antibody. We propose an overlap of this antibody-binding region with the binding epitope for V-set and Ig domain containing 3 (VSIG3), a purported functional binding partner of VISTA. The structure and functional epitope presented here will help guide future drug development efforts against this important checkpoint target.
Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation.,Mehta N, Maddineni S, Mathews II, Andres Parra Sperberg R, Huang PS, Cochran JR Cell Rep. 2019 Sep 3;28(10):2509-2516.e5. doi: 10.1016/j.celrep.2019.07.073. PMID:31484064[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sakr MA, Takino T, Domoto T, Nakano H, Wong RW, Sasaki M, Nakanuma Y, Sato H. GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase. Cancer Sci. 2010 Nov;101(11):2368-74. doi: 10.1111/j.1349-7006.2010.01675.x. PMID:20666777 doi:http://dx.doi.org/10.1111/j.1349-7006.2010.01675.x
- ↑ Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R. VISTA is an immune checkpoint molecule for human T cells. Cancer Res. 2014 Apr 1;74(7):1924-32. doi: 10.1158/0008-5472.CAN-13-1504. PMID:24691993 doi:http://dx.doi.org/10.1158/0008-5472.CAN-13-1504
- ↑ Mehta N, Maddineni S, Mathews II, Andres Parra Sperberg R, Huang PS, Cochran JR. Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation. Cell Rep. 2019 Sep 3;28(10):2509-2516.e5. doi: 10.1016/j.celrep.2019.07.073. PMID:31484064 doi:http://dx.doi.org/10.1016/j.celrep.2019.07.073
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