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4dfi

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Crystal structure of cell adhesion molecule nectin-2/CD112 mutant FAMP

Structural highlights

4dfi is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
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/4dfi"

@@ Line 1: / Line 1: @@
-[[Image:4dfi.jpg|left|200px]]
-<!--
+==Crystal structure of cell adhesion molecule nectin-2/CD112 mutant FAMP==
-The line below this paragraph, containing "STRUCTURE_4dfi", creates the "Structure Box" on the page.
+<StructureSection load='4dfi' size='340' side='right'caption='[[4dfi]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[4dfi]] is a 1 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=4DFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DFI FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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=4dfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dfi OCA], [https://pdbe.org/4dfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dfi RCSB], [https://www.ebi.ac.uk/pdbsum/4dfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dfi ProSAT]</span></td></tr>
-{{STRUCTURE_4dfi|  PDB=4dfi  |  SCENE=  }}
+</table>
+== Function ==
+[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 ==
+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 mutant FAMP===
+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<ref>PMID:22547693</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4dfi" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22547693}}, adds the Publication Abstract to the page
+*[[Poliovirus receptor-related protein|Poliovirus receptor-related protein]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22547693 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22547693}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[4dfi]] is a 1 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=4DFI OCA].
-==Reference==
-<ref group="xtra">PMID:022547693</ref><references group="xtra"/>
 [[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: Cd226]]
+[[Category: Zhang S]]
-[[Category: Cell adhesion]]
-[[Category: Cell surface]]

4dfi

From Proteopedia

Current revision

Crystal structure of cell adhesion molecule nectin-2/CD112 mutant FAMP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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