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4dfh

From Proteopedia

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Crystal structure of cell adhesion molecule nectin-2/CD112 variable domain

Structural highlights

4dfh is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NECT2_HUMAN] Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive (PubMed:26755705). Probable cell adhesion protein (PubMed:9657005).^[1] ^[2] (Microbial infection) Acts as a receptor for herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV).^[3] ^[4]

Publication Abstract from PubMed

The nectin and nectin-like molecule (Necl) family includes important cell adhesion molecules (CAMs) characterized by their Ig-like nature. Such CAMs regulate a broad spectrum of cell-cell interactions, including the interaction between NK cells and cytotoxic T lymphocytes (CTLs) and their target cells. CAM members nectin-2 (CD112) and Necl-5 (CD155) are believed to form homodimers (for nectin-2) or heterodimers in their functions for cell adhesion, as well as to interact with immune costimulatory receptor DNAX accessory molecule 1 (DNAM-1) (CD226) to regulate functions of both NK and CTL cells. However, the structural basis of the interactive mode of DNAM-1 with nectin-2 or Necl-5 is not yet understood. In this study, a soluble nectin-2 Ig-like V-set domain (nectin-2v) was successfully prepared and demonstrated to bind to both soluble ectodomain and cell surface-expressed full-length DNAM-1. The 1.85-A crystal structure of nectin-2v displays a perpendicular homodimer arrangement, revealing the homodimer characteristics of the nectin and Necls. Further mutational analysis indicated that disruption of the homodimeric interface of nectin-2v led to a failure of the homodimer formation, as confirmed by crystal structure and biochemical properties of the mutant protein of nectin-2v. Interestingly, the monomer mutant also loses DNAM-1 binding, as evidenced by cell staining with tetramers and surface plasmon resonance assays. The data indicate that interaction with DNAM-1 requires either the homodimerization or engagement of the homodimeric interface of nectin-2v. These results have implications for immune intervention of tumors or autoimmune diseases in the DNAM-1/nectin-2-dependent pathway.

Crystal Structure of Cell Adhesion Molecule Nectin-2/CD112 and Its Binding to Immune Receptor DNAM-1/CD226.,Liu J, Qian X, Chen Z, Xu X, Gao F, Zhang S, Zhang R, Qi J, Gao GF, Yan J J Immunol. 2012 Jun 1;188(11):5511-20. Epub 2012 Apr 30. PMID:22547693^[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
↑ Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, Xu R, Eisenberg RJ, Cohen GH, Spear PG. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology. 1998 Jun 20;246(1):179-89. PMID:9657005 doi:http://dx.doi.org/10.1006/viro.1998.9218
↑ Martinez WM, Spear PG. Structural features of nectin-2 (HveB) required for herpes simplex virus entry. J Virol. 2001 Nov;75(22):11185-95. PMID:11602758 doi:http://dx.doi.org/10.1128/JVI.75.22.11185-11195.2001
↑ Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, Xu R, Eisenberg RJ, Cohen GH, Spear PG. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology. 1998 Jun 20;246(1):179-89. PMID:9657005 doi:http://dx.doi.org/10.1006/viro.1998.9218
↑ Liu J, Qian X, Chen Z, Xu X, Gao F, Zhang S, Zhang R, Qi J, Gao GF, Yan J. Crystal Structure of Cell Adhesion Molecule Nectin-2/CD112 and Its Binding to Immune Receptor DNAM-1/CD226. J Immunol. 2012 Jun 1;188(11):5511-20. Epub 2012 Apr 30. PMID:22547693 doi:10.4049/jimmunol.1200324

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dfh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of cell adhesion molecule nectin-2/CD112 variable domain==
-<StructureSection load='4dfh' size='340' side='right' caption='[[4dfh]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+<StructureSection load='4dfh' size='340' side='right'caption='[[4dfh]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dfh]] is a 2 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=4DFH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DFH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dfh]] is a 2 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=4DFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DFH FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dfi|4dfi]]</td></tr>
+</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=4dfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dfh OCA], [https://pdbe.org/4dfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dfh RCSB], [https://www.ebi.ac.uk/pdbsum/4dfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dfh ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HVEB, PRR2, PVRL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</table>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dfh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dfh RCSB], [http://www.ebi.ac.uk/pdbsum/4dfh PDBsum]</span></td></tr>
+== Function ==
-<table>
+[[https://www.uniprot.org/uniprot/NECT2_HUMAN NECT2_HUMAN]] Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive (PubMed:26755705). Probable cell adhesion protein (PubMed:9657005).<ref>PMID:26755705</ref> <ref>PMID:9657005</ref>   (Microbial infection) Acts as a receptor for herpes simplex virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies virus (PRV).<ref>PMID:11602758</ref> <ref>PMID:9657005</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dfh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Poliovirus receptor-related protein|Poliovirus receptor-related protein]]
 == References ==
 <references/>
@@ Line 20: / Line 25: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Chen, Z.]]
+[[Category: Large Structures]]
-[[Category: Gao, F.]]
+[[Category: Chen Z]]
-[[Category: Gao, G F.]]
+[[Category: Gao F]]
-[[Category: Liu, J.]]
+[[Category: Gao GF]]
-[[Category: Qi, J.]]
+[[Category: Liu J]]
-[[Category: Qian, X.]]
+[[Category: Qi J]]
-[[Category: Xu, X.]]
+[[Category: Qian X]]
-[[Category: Yan, J.]]
+[[Category: Xu X]]
-[[Category: Zhang, R.]]
+[[Category: Yan J]]
-[[Category: Zhang, S.]]
+[[Category: Zhang R]]
-[[Category: Cell adhesion]]
+[[Category: Zhang S]]
-[[Category: Cell surface]]
-[[Category: Dnam-1]]

4dfh

From Proteopedia

Current revision

Crystal structure of cell adhesion molecule nectin-2/CD112 variable domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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