6o3o

From Proteopedia

(Difference between revisions)

Revision as of 16:01, 28 August 2019

Structure of human DNAM-1 (CD226) bound to nectin-like protein-5 (necl-5)

Structural highlights

6o3o 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:	CD226, DNAM1 (HUMAN), PVR, PVS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] [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.^[3] ^[4]

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^[5]

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

References

↑ Zhu Y, Paniccia A, Schulick AC, Chen W, Koenig MR, Byers JT, Yao S, Bevers S, Edil BH. Identification of CD112R as a novel checkpoint for human T cells. J Exp Med. 2016 Feb 8;213(2):167-76. doi: 10.1084/jem.20150785. Epub 2016 Jan 11. PMID:26755705 doi:http://dx.doi.org/10.1084/jem.20150785
↑ Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, Kitamura T, Nicholl J, Sutherland GR, Lanier LL, Phillips JH. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996 Jun;4(6):573-81. PMID:8673704
↑ 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
↑ Deuss FA, Watson GM, Goodall KJ, Leece I, Chatterjee S, Fu Z, Thaysen-Andersen M, Andrews DM, Rossjohn J, Berry R. Structural basis for the recognition of nectin-like protein-5 by the human activating immune receptor, DNAM-1. J Biol Chem. 2019 Jun 28. pii: RA119.009261. doi: 10.1074/jbc.RA119.009261. PMID:31253644 doi:http://dx.doi.org/10.1074/jbc.RA119.009261

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/6o3o"

@@ Line 3: / Line 3: @@
 <StructureSection load='6o3o' size='340' side='right'caption='[[6o3o]], [[Resolution|resolution]] 2.80&Aring;' 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>
+<table><tr><td colspan='2'>[[6o3o]] 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=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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD226, DNAM1 ([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=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>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Berry, R]]

6o3o

From Proteopedia

Revision as of 16:01, 28 August 2019

Structure of human DNAM-1 (CD226) bound to nectin-like protein-5 (necl-5)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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