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| | ==complex structure of mCD226-ecto and hCD155-D1== | | ==complex structure of mCD226-ecto and hCD155-D1== |
| - | <StructureSection load='6isc' size='340' side='right' caption='[[6isc]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='6isc' size='340' side='right'caption='[[6isc]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6isc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ISC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ISC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6isc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=6ISC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ISC 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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd226, Pta1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), PVR, PVS ([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=6isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isc OCA], [http://pdbe.org/6isc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6isc RCSB], [http://www.ebi.ac.uk/pdbsum/6isc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6isc 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=6isc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isc OCA], [https://pdbe.org/6isc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6isc RCSB], [https://www.ebi.ac.uk/pdbsum/6isc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6isc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CD226_MOUSE CD226_MOUSE]] Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell. Cell surface receptor for NECTIN2. Upon ligand binding, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Competes with PVRIG for NECTIN2-binding.[UniProtKB:Q15762] [[http://www.uniprot.org/uniprot/PVR_HUMAN PVR_HUMAN]] Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. Serves as a receptor for poliovirus attachment to target cells. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport.<ref>PMID:15471548</ref> <ref>PMID:15607800</ref> | + | [https://www.uniprot.org/uniprot/CD226_MOUSE CD226_MOUSE] Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell. Cell surface receptor for NECTIN2. Upon ligand binding, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Competes with PVRIG for NECTIN2-binding.[UniProtKB:Q15762] |
| | <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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Gao, G F]] | + | [[Category: Mus musculus]] |
| - | [[Category: Li, Y]] | + | [[Category: Gao GF]] |
| - | [[Category: Qi, J]] | + | [[Category: Li Y]] |
| - | [[Category: Tan, S]] | + | [[Category: Qi J]] |
| - | [[Category: Wang, H]] | + | [[Category: Tan S]] |
| - | [[Category: Zhang, S]] | + | [[Category: Wang H]] |
| - | [[Category: Cd155]]
| + | [[Category: Zhang S]] |
| - | [[Category: Complex structure]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mcd226]]
| + | |
| - | [[Category: Nk cell receptor]]
| + | |
| Structural highlights
Function
CD226_MOUSE Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell. Cell surface receptor for NECTIN2. Upon ligand binding, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Competes with PVRIG for NECTIN2-binding.[UniProtKB:Q15762]
Publication Abstract from PubMed
Natural killer (NK) cells are important component of innate immunity and also contribute to activating and reshaping the adaptive immune responses. The functions of NK cells are modulated by multiple inhibitory and stimulatory receptors. Among these receptors, the activating receptor CD226 (DNAM-1) mediates NK cell activation via binding to its nectin-like (Necl) family ligand, CD155 (Necl-5). Here, we present a unique side-by-side arrangement pattern of two tandem immunoglobulin V-set (IgV) domains deriving from the ectodomains of both human CD226 (hCD226-ecto) and mouse CD226 (mCD226-ecto), which is substantially different from the conventional head-to-tail arrangement of other multiple Ig-like domain molecules. The hybrid complex structure of mCD226-ecto binding to the first domain of human CD155 (hCD155-D1) reveals a conserved binding interface with the first domain of CD226 (D1), whereas the second domain of CD226 (D2) both provides structural supports for the unique architecture of CD226 and forms direct interactions with CD155. In the absence of the D2 domain, CD226-D1 exhibited substantially reduced binding efficacy to CD155. Collectively, these findings would broaden our knowledge of the interaction between NK cell receptors and the nectin/Necl family ligands, as well as provide molecular basis for the development of CD226-targeted antitumor immunotherapeutics.
Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5.,Wang H, Qi J, Zhang S, Li Y, Tan S, Gao GF Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):988-996. doi:, 10.1073/pnas.1815716116. Epub 2018 Dec 27. PMID:30591568[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang H, Qi J, Zhang S, Li Y, Tan S, Gao GF. Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):988-996. doi:, 10.1073/pnas.1815716116. Epub 2018 Dec 27. PMID:30591568 doi:http://dx.doi.org/10.1073/pnas.1815716116
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