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| | ==Structure of TIGIT bound to nectin-2 (CD112)== | | ==Structure of TIGIT bound to nectin-2 (CD112)== |
| - | <StructureSection load='5v52' size='340' side='right' caption='[[5v52]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='5v52' size='340' side='right'caption='[[5v52]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v52]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V52 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V52 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v52]] is a 4 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=5V52 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V52 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.1Å</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=5v52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v52 OCA], [http://pdbe.org/5v52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v52 RCSB], [http://www.ebi.ac.uk/pdbsum/5v52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v52 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5v52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v52 OCA], [https://pdbe.org/5v52 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v52 RCSB], [https://www.ebi.ac.uk/pdbsum/5v52 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v52 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIGIT_HUMAN TIGIT_HUMAN]] Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. [[http://www.uniprot.org/uniprot/NECT2_HUMAN NECT2_HUMAN]] Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive (PubMed:26755705). Probable cell adhesion protein (PubMed:9657005).<ref>PMID:26755705</ref> <ref>PMID:9657005</ref> (Microbial infection) Acts as a receptor for herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV).<ref>PMID:11602758</ref> <ref>PMID:9657005</ref> | + | [https://www.uniprot.org/uniprot/TIGIT_HUMAN TIGIT_HUMAN] Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. |
| | <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: Berry, R]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Deuss, F A]] | + | [[Category: Large Structures]] |
| - | [[Category: Gully, B S]] | + | [[Category: Berry R]] |
| - | [[Category: Rossjohn, J]] | + | [[Category: Deuss FA]] |
| - | [[Category: Adhesion molecule]] | + | [[Category: Gully BS]] |
| - | [[Category: Immune receptor]] | + | [[Category: Rossjohn J]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin fold]]
| + | |
| Structural highlights
Function
TIGIT_HUMAN Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells.
Publication Abstract from PubMed
T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin-like adhesion molecules and thus plays a critical role in the innate immune response to malignant transformation. Although the TIGIT nectin-like protein-5 (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor that is broadly over-expressed in breast and ovarian cancer, remains unknown. Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is most distal from the membrane with an affinity of 6 mum, which was moderately lower than the affinity observed for the TIGIT/necl-5 interaction (3.2 mum). The TIGIT/nectin-2 binding disrupted pre-assembled nectin-2 oligomers, suggesting that receptor-ligand and ligand-ligand associations are mutually exclusive events. Indeed, the crystal structure of TIGIT bound to the first immunoglobulin domain of nectin-2 indicated that the receptor and ligand dock using the same molecular surface and a conserved "lock and key" binding motifs previously observed to mediate nectin/nectin homotypic interactions as well as TIGIT/necl-5 recognition. Using a mutagenesis approach, we dissected the energetic basis for the TIGIT/nectin-2 interaction and revealed that an "aromatic key" of nectin-2 is critical for this interaction, whereas variations in the lock were tolerated. Moreover, we found that the C-C' loop of the ligand dictates the TIGIT binding hierarchy. Altogether, these findings broaden our understanding of nectin/nectin receptor interactions and have implications for better understanding the molecular basis for autoimmune disease and cancer.
Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT).,Deuss FA, Gully BS, Rossjohn J, Berry R J Biol Chem. 2017 Jul 7;292(27):11413-11422. doi: 10.1074/jbc.M117.786483. Epub, 2017 May 17. PMID:28515320[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Deuss FA, Gully BS, Rossjohn J, Berry R. Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT). J Biol Chem. 2017 Jul 7;292(27):11413-11422. doi: 10.1074/jbc.M117.786483. Epub, 2017 May 17. PMID:28515320 doi:http://dx.doi.org/10.1074/jbc.M117.786483
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