3o8e
From Proteopedia
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{{STRUCTURE_3o8e| PDB=3o8e | SCENE= }} | {{STRUCTURE_3o8e| PDB=3o8e | SCENE= }} | ||
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===Structure of extracelllar portion of CD46 in complex with Adenovirus type 11 knob=== | ===Structure of extracelllar portion of CD46 in complex with Adenovirus type 11 knob=== | ||
| + | {{ABSTRACT_PUBMED_20941397}} | ||
| + | ==Disease== | ||
| + | [[http://www.uniprot.org/uniprot/MCP_HUMAN MCP_HUMAN]] Defects in CD46 are a cause of susceptibility to hemolytic uremic syndrome atypical type 2 (AHUS2) [MIM:[http://omim.org/entry/612922 612922]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.<ref>PMID:14615110</ref><ref>PMID:14566051</ref><ref>PMID:16621965</ref><ref>PMID:16386793</ref><ref>PMID:20513133</ref> | ||
| - | + | ==Function== | |
| - | + | [[http://www.uniprot.org/uniprot/MCP_HUMAN MCP_HUMAN]] Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. A number of viral and bacterial pathogens seem to exploit this property and directly induce an immunosuppressive phenotype in T-cells by binding to CD46.<ref>PMID:10843656</ref><ref>PMID:12540904</ref> | |
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==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | <ref group="xtra">PMID:020941397</ref><references group="xtra"/> | + | <ref group="xtra">PMID:020941397</ref><references group="xtra"/><references/> |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Human adenovirus 11]] | [[Category: Human adenovirus 11]] | ||
Revision as of 04:33, 25 March 2013
Contents |
Structure of extracelllar portion of CD46 in complex with Adenovirus type 11 knob
Template:ABSTRACT PUBMED 20941397
Disease
[MCP_HUMAN] Defects in CD46 are a cause of susceptibility to hemolytic uremic syndrome atypical type 2 (AHUS2) [MIM:612922]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.[1][2][3][4][5]
Function
[MCP_HUMAN] Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. A number of viral and bacterial pathogens seem to exploit this property and directly induce an immunosuppressive phenotype in T-cells by binding to CD46.[6][7]
About this Structure
3o8e is a 4 chain structure with sequence from Homo sapiens and Human adenovirus 11. Full crystallographic information is available from OCA.
Reference
- Persson BD, Schmitz NB, Santiago C, Zocher G, Larvie M, Scheu U, Casasnovas JM, Stehle T. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens. PLoS Pathog. 2010 Sep 30;6(9). pii: e1001122. PMID:20941397 doi:10.1371/journal.ppat.1001122
- ↑ Noris M, Brioschi S, Caprioli J, Todeschini M, Bresin E, Porrati F, Gamba S, Remuzzi G. Familial haemolytic uraemic syndrome and an MCP mutation. Lancet. 2003 Nov 8;362(9395):1542-7. PMID:14615110 doi:10.1016/S0140-6736(03)14742-3
- ↑ Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Muslumanoglu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, Goodship TH. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12966-71. Epub 2003 Oct 17. PMID:14566051 doi:10.1073/pnas.2135497100
- ↑ Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, Mele C, Bresin E, Cassis L, Gamba S, Porrati F, Bucchioni S, Monteferrante G, Fang CJ, Liszewski MK, Kavanagh D, Atkinson JP, Remuzzi G. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006 Aug 15;108(4):1267-79. Epub 2006 Apr 18. PMID:16621965 doi:10.1182/blood-2005-10-007252
- ↑ Esparza-Gordillo J, Jorge EG, Garrido CA, Carreras L, Lopez-Trascasa M, Sanchez-Corral P, de Cordoba SR. Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree. Mol Immunol. 2006 Apr;43(11):1769-75. Epub 2006 Jan 18. PMID:16386793 doi:10.1016/j.molimm.2005.11.008
- ↑ Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256. PMID:20513133 doi:10.1002/humu.21256
- ↑ Astier A, Trescol-Biemont MC, Azocar O, Lamouille B, Rabourdin-Combe C. Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation. J Immunol. 2000 Jun 15;164(12):6091-5. PMID:10843656
- ↑ Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature. 2003 Jan 23;421(6921):388-92. PMID:12540904 doi:10.1038/nature01315
Categories: Homo sapiens | Human adenovirus 11 | Casasnovas, J M. | Persson, B D. | Schmitz, N B. | Stehle, T. | Adenovirus | Cd46 | Cell adhesion - immune system complex | Cell adhesion-immune system complex | Cell adhesion-immunity complex | Complement control protein | Fiber knob | Short consensus repeat | Virus-receptor interaction
