View source for 5v52


==Structure of TIGIT bound to nectin-2 (CD112)==
<StructureSection load='5v52' size='340' side='right'caption='[[5v52]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</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>
== Function ==
[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.
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== 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<ref>PMID:28515320</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5v52" style="background-color:#fffaf0;"></div>

==See Also==
*[[Poliovirus receptor-related protein|Poliovirus receptor-related protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Berry R]]
[[Category: Deuss FA]]
[[Category: Gully BS]]
[[Category: Rossjohn J]]