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3ff8

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Revision as of 06:40, 1 November 2017

Structure of NK cell receptor KLRG1 bound to E-cadherin

Structural highlights

3ff8 is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3ff7, 3ff9
Gene:	CDH1, CDHE, UVO (HUMAN), Klrg1, Mafa (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CADH1_HUMAN] Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM:137215]. An autosomal dominant cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.^[1] ^[2] Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]. Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.

Function

[CADH1_HUMAN] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.^[3] E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.^[4] [KLRG1_MOUSE] Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands. May mediate missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of E-cadherin/CDH1, N-cadherin/CDH2 and R-cadherin/CDH4 on target cells.^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of missing self recognition have focused on NK receptors that bind MHC. However, NK cells also possess inhibitory receptors specific for non-MHC ligands, notably cadherins, which are downregulated in metastatic tumors. We determined the structure of killer cell lectin-like receptor G1 (KLRG1) in complex with E-cadherin. KLRG1 mediates missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of several cadherins (E-, N-, and R-) on target cells. This site overlaps the site responsible for cell-cell adhesion but is distinct from the integrin alpha(E)beta(7) binding site. We propose that E-cadherin may coengage KLRG1 and alpha(E)beta(7) and that KLRG1 overcomes its exceptionally weak affinity for cadherins through multipoint attachment to target cells, resulting in inhibitory signaling.

Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.,Li Y, Hofmann M, Wang Q, Teng L, Chlewicki LK, Pircher H, Mariuzza RA Immunity. 2009 Jul 17;31(1):35-46. PMID:19604491^[6]

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

References

↑ Yoon KA, Ku JL, Yang HK, Kim WH, Park SY, Park JG. Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Hum Genet. 1999;44(3):177-80. PMID:10319582 doi:10.1007/s100380050137
↑ Yabuta T, Shinmura K, Tani M, Yamaguchi S, Yoshimura K, Katai H, Nakajima T, Mochiki E, Tsujinaka T, Takami M, Hirose K, Yamaguchi A, Takenoshita S, Yokota J. E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer. Int J Cancer. 2002 Oct 10;101(5):434-41. PMID:12216071 doi:10.1002/ijc.10633
↑ Agiostratidou G, Muros RM, Shioi J, Marambaud P, Robakis NK. The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors. J Neurochem. 2006 Feb;96(4):1182-8. Epub 2006 Jan 26. PMID:16417575 doi:JNC3616
↑ Agiostratidou G, Muros RM, Shioi J, Marambaud P, Robakis NK. The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors. J Neurochem. 2006 Feb;96(4):1182-8. Epub 2006 Jan 26. PMID:16417575 doi:JNC3616
↑ Li Y, Hofmann M, Wang Q, Teng L, Chlewicki LK, Pircher H, Mariuzza RA. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity. 2009 Jul 17;31(1):35-46. PMID:19604491 doi:S1074-7613(09)00276-3
↑ Li Y, Hofmann M, Wang Q, Teng L, Chlewicki LK, Pircher H, Mariuzza RA. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity. 2009 Jul 17;31(1):35-46. PMID:19604491 doi:S1074-7613(09)00276-3

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ff8"

@@ Line 1: / Line 1: @@
 ==Structure of NK cell receptor KLRG1 bound to E-cadherin==
 <StructureSection load='3ff8' size='340' side='right' caption='[[3ff8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ff7|3ff7]], [[3ff9|3ff9]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDH1, CDHE, UVO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Klrg1, Mafa ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3ff8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ff8 OCA], [http://pdbe.org/3ff8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ff8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ff8 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=3ff8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ff8 OCA], [http://pdbe.org/3ff8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ff8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ff8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ff8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 3ff8" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Cadherin|Cadherin]]
 == References ==
 <references/>
@@ Line 42: / Line 40: @@
 [[Category: Li, Y]]
 [[Category: Mariuzza, R A]]
+[[Category: Calcium]]
 [[Category: Cell adhesion]]
 [[Category: Cell adhesion-immune system complex]]
@@ Line 53: / Line 52: @@
 [[Category: Membrane]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Receptor]]
 [[Category: Signal-anchor]]
 [[Category: Transmembrane]]

3ff8

From Proteopedia

Revision as of 06:40, 1 November 2017

Structure of NK cell receptor KLRG1 bound to E-cadherin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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