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4h5s

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Revision as of 18:14, 5 August 2016

Complex structure of Necl-2 and CRTAM

Structural highlights

4h5s is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CRTAM (HUMAN), CADM1, IGSF4, IGSF4A, NECL2, SYNCAM, TSLC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CRTAM_HUMAN] Interaction with CADM1 promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo.^[1] [UniProtKB:Q149L7] [CADM1_HUMAN] Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Also mediates heterophilic cell-cell adhesion with CADM3 and PVRL3 in a Ca(2+)-independent manner. Acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo. May contribute to the less invasive phenotypes of lepidic growth tumor cells. In mast cells, may mediate attachment to and promote communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. May act as a synaptic cell adhesion molecule that drives synapse assembly. May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons. May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] [UniProtKB:Q8R5M8]

Publication Abstract from PubMed

Nectin and nectin-like proteins are cell adhesion molecules that mediate the formation of cell adherens junctions by forming homo- or heterodimers. Some members of this protein family can also be used by immune receptors to mediate immune recognition. For instance, nectin-like 2 (Necl-2) is used as a ligand for the immune system by interaction with the immune receptor CRTAM (class-I MHC-restricted T cell associated molecule), which is mainly expressed on the surface of cytotoxic lymphocyte cells. However, the Necl-2/CRTAM binding mode and its relationship to cell adhesion are not known. Here, we report a Necl-2/CRTAM complex structure, demonstrating that Necl-2 binding to CRTAM competes with the dimerization of CRTAM and possibly Necl-2. Necl-2 occupies the CRTAM homodimer interface, making homodimerization impossible. Mutational and functional analyses identified key amino acids (double "lock-and-key") responsible for the binding. Our work illustrates how the cell adhesion molecule Necl-2 competitively binds the immune receptor CRTAM.

Competition of Cell Adhesion and Immune Recognition: Insights into the Interaction between CRTAM and Nectin-like 2.,Zhang S, Lu G, Qi J, Li Y, Zhang Z, Zhang B, Fan Z, Yan J, Gao GF Structure. 2013 Jul 16. pii: S0969-2126(13)00207-4. doi:, 10.1016/j.str.2013.06.006. PMID:23871486^[8]

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

References

↑ Boles KS, Barchet W, Diacovo T, Cella M, Colonna M. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood. 2005 Aug 1;106(3):779-86. Epub 2005 Apr 5. PMID:15811952 doi:10.1182/blood-2005-02-0817
↑ Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, Sekiya T, Reeves RH, Murakami Y. TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet. 2001 Apr;27(4):427-30. PMID:11279526 doi:10.1038/86934
↑ Yageta M, Kuramochi M, Masuda M, Fukami T, Fukuhara H, Maruyama T, Shibuya M, Murakami Y. Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer. Cancer Res. 2002 Sep 15;62(18):5129-33. PMID:12234973
↑ Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y. The tumor suppressor protein TSLC1 is involved in cell-cell adhesion. J Biol Chem. 2002 Aug 23;277(34):31014-9. Epub 2002 Jun 5. PMID:12050160 doi:10.1074/jbc.M203620200
↑ Ito A, Okada M, Uchino K, Wakayama T, Koma Y, Iseki S, Tsubota N, Okita Y, Kitamura Y. Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioloalveolar carcinoma. Lab Invest. 2003 Aug;83(8):1175-83. PMID:12920246
↑ Boles KS, Barchet W, Diacovo T, Cella M, Colonna M. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood. 2005 Aug 1;106(3):779-86. Epub 2005 Apr 5. PMID:15811952 doi:10.1182/blood-2005-02-0817
↑ Furuno T, Ito A, Koma Y, Watabe K, Yokozaki H, Bienenstock J, Nakanishi M, Kitamura Y. The spermatogenic Ig superfamily/synaptic cell adhesion molecule mast-cell adhesion molecule promotes interaction with nerves. J Immunol. 2005 Jun 1;174(11):6934-42. PMID:15905536
↑ Zhang S, Lu G, Qi J, Li Y, Zhang Z, Zhang B, Fan Z, Yan J, Gao GF. Competition of Cell Adhesion and Immune Recognition: Insights into the Interaction between CRTAM and Nectin-like 2. Structure. 2013 Jul 16. pii: S0969-2126(13)00207-4. doi:, 10.1016/j.str.2013.06.006. PMID:23871486 doi:10.1016/j.str.2013.06.006

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/4h5s"

@@ Line 1: / Line 1: @@
 ==Complex structure of Necl-2 and CRTAM==
 <StructureSection load='4h5s' size='340' side='right' caption='[[4h5s]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4h5s]] is a 2 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=4H5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H5S FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CRTAM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CADM1, IGSF4, IGSF4A, NECL2, SYNCAM, TSLC1 ([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=4h5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h5s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h5s RCSB], [http://www.ebi.ac.uk/pdbsum/4h5s 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=4h5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h5s OCA], [http://pdbe.org/4h5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h5s RCSB], [http://www.ebi.ac.uk/pdbsum/4h5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h5s ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4h5s" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4h5s

From Proteopedia

Revision as of 18:14, 5 August 2016

Complex structure of Necl-2 and CRTAM

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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