| Structural highlights
1o6s is a 2 chain structure with sequence from Homo sapiens and Listeria monocytogenes egd-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 1o6t, 1o6v |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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]
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
Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells by inducing its own phagocytosis. The listerial protein internalin (InlA) mediates bacterial adhesion and invasion of epithelial cells in the human intestine through specific interaction with its host cell receptor E-cadherin. We present the crystal structures of the functional domain of InlA alone and in a complex with the extracellular, N-terminal domain of human E-cadherin (hEC1). The leucine rich repeat (LRR) domain of InlA surrounds and specifically recognizes hEC1. Individual interactions were probed by mutagenesis and analytical ultracentrifugation. These include Pro16 of hEC1, a major determinant for human susceptibility to L. monocytogenes infection that is essential for intermolecular recognition. Our studies reveal the structural basis for host tro-pism of this bacterium and the molecular deception L. monocytogenes employs to exploit the E-cadherin system.
Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin.,Schubert WD, Urbanke C, Ziehm T, Beier V, Machner MP, Domann E, Wehland J, Chakraborty T, Heinz DW Cell. 2002 Dec 13;111(6):825-36. PMID:12526809[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Schubert WD, Urbanke C, Ziehm T, Beier V, Machner MP, Domann E, Wehland J, Chakraborty T, Heinz DW. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell. 2002 Dec 13;111(6):825-36. PMID:12526809
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