6o3o
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of human DNAM-1 (CD226) bound to nectin-like protein-5 (necl-5)== | |
| + | <StructureSection load='6o3o' size='340' side='right'caption='[[6o3o]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6o3o]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O3O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O3O FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o3o OCA], [http://pdbe.org/6o3o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o3o RCSB], [http://www.ebi.ac.uk/pdbsum/6o3o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o3o ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CD226_HUMAN CD226_HUMAN]] Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell (PubMed:8673704). 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 (PubMed:26755705).<ref>PMID:26755705</ref> <ref>PMID:8673704</ref> [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Nectin and nectin-like (NECL) adhesion molecules are broadly overexpressed in a wide range of cancers. By binding to these adhesion molecules, the immunoreceptors DNAX accessory molecule-1 (DNAM-1), CD96 molecule (CD96), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) play a crucial role in regulating the anticancer activities of immune effector cells. However, within this axis, it remains unclear how DNAM-1 recognizes its cognate ligands. Here, we determined the structure of human DNAM-1 in complex with nectin-like protein-5 (NECL-5) at 2.8 A resolution. Unexpectedly, we found that the two extracellular domains (D1-D2) of DNAM-1 adopt an unconventional "collapsed" arrangement that is markedly distinct from those in other immunoglobulin-based immunoreceptors. The DNAM-1:NECL-5 interaction was underpinned by conserved lock-and-key motifs located within their respective D1 domains, but also included a distinct interface derived from DNAM-1 D2. Mutation of the signature DNAM-1 "key" motif within the D1 domain attenuated NECL-5 binding and natural killer cell-mediated cytotoxicity. Altogether, our results have implications for understanding the binding mode of an immune receptor family that is emerging as a viable candidate for cancer immunotherapy. | ||
| - | + | Structural basis for the recognition of nectin-like protein-5 by the human activating immune receptor, DNAM-1.,Deuss FA, Watson GM, Goodall KJ, Leece I, Chatterjee S, Fu Z, Thaysen-Andersen M, Andrews DM, Rossjohn J, Berry R J Biol Chem. 2019 Jun 28. pii: RA119.009261. doi: 10.1074/jbc.RA119.009261. PMID:31253644<ref>PMID:31253644</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6o3o" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Berry, R]] | ||
| + | [[Category: Deuss, F A]] | ||
| + | [[Category: Rossjohn, J]] | ||
| + | [[Category: Watson, G M]] | ||
| + | [[Category: Adhesion molecule]] | ||
| + | [[Category: Immune receptor]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Immunoglobulin domain]] | ||
Revision as of 05:49, 10 July 2019
Structure of human DNAM-1 (CD226) bound to nectin-like protein-5 (necl-5)
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