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3udw

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Revision as of 11:28, 5 August 2016

Crystal structure of the immunoreceptor TIGIT in complex with Poliovirus receptor (PVR/CD155/necl-5) D1 domain

Structural highlights

3udw is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	TIGIT, VSIG9, VSTM3 (HUMAN), PVR, PVS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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. [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.^[1] ^[2]

Publication Abstract from PubMed

Nectins (nectin1-4) and Necls [nectin-like (Necl1-5)] are Ig superfamily cell adhesion molecules that regulate cell differentiation and tissue morphogenesis. Adherens junction formation and subsequent cell-cell signaling is initiated by the assembly of higher-order receptor clusters of cognate molecules on juxtaposed cells. However, the structural and mechanistic details of signaling cluster formation remain unclear. Here, we report the crystal structure of poliovirus receptor (PVR)/Nectin-like-5/CD155) in complex with its cognate immunoreceptor ligand T-cell-Ig-and-ITIM-domain (TIGIT). The TIGIT/PVR interface reveals a conserved specific "lock-and-key" interaction. Notably, two TIGIT/PVR dimers assemble into a heterotetramer with a core TIGIT/TIGIT cis-homodimer, each TIGIT molecule binding one PVR molecule. Structure-guided mutations that disrupt the TIGIT/TIGIT interface limit both TIGIT/PVR-mediated cell adhesion and TIGIT-induced PVR phosphorylation in primary dendritic cells. Our data suggest a cis-trans receptor clustering mechanism for cell adhesion and signaling by the TIGIT/PVR complex and provide structural insights into how the PVR family of immunoregulators function.

Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering.,Stengel KF, Harden-Bowles K, Yu X, Rouge L, Yin J, Comps-Agrar L, Wiesmann C, Bazan JF, Eaton DL, Grogan JL Proc Natl Acad Sci U S A. 2012 Mar 15. PMID:22421438^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sloan KE, Eustace BK, Stewart JK, Zehetmeier C, Torella C, Simeone M, Roy JE, Unger C, Louis DN, Ilag LL, Jay DG. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration. BMC Cancer. 2004 Oct 7;4:73. PMID:15471548 doi:1471-2407-4-73
↑ Pende D, Bottino C, Castriconi R, Cantoni C, Marcenaro S, Rivera P, Spaggiari GM, Dondero A, Carnemolla B, Reymond N, Mingari MC, Lopez M, Moretta L, Moretta A. PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol. 2005 Feb;42(4):463-9. PMID:15607800 doi:10.1016/j.molimm.2004.07.028
↑ Stengel KF, Harden-Bowles K, Yu X, Rouge L, Yin J, Comps-Agrar L, Wiesmann C, Bazan JF, Eaton DL, Grogan JL. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering. Proc Natl Acad Sci U S A. 2012 Mar 15. PMID:22421438 doi:10.1073/pnas.1120606109

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3udw"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the immunoreceptor TIGIT in complex with Poliovirus receptor (PVR/CD155/necl-5) D1 domain==
 <StructureSection load='3udw' size='340' side='right' caption='[[3udw]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3udw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UDW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UDW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3udw]] is a 4 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=3UDW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UDW 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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIGIT, VSIG9, VSTM3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PVR, PVS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIGIT, VSIG9, VSTM3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PVR, PVS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3udw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3udw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3udw RCSB], [http://www.ebi.ac.uk/pdbsum/3udw PDBsum]</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=3udw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3udw OCA], [http://pdbe.org/3udw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3udw RCSB], [http://www.ebi.ac.uk/pdbsum/3udw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3udw ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3udw" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Bazan, F J]]
 [[Category: Rouge, L]]

3udw

From Proteopedia

Revision as of 11:28, 5 August 2016

Crystal structure of the immunoreceptor TIGIT in complex with Poliovirus receptor (PVR/CD155/necl-5) D1 domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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