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Human Adenovirus type 11 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)Human Adenovirus type 11 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)
Structural highlights
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[SPIKE_ADE1P] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. [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] 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 PubMedAdenoviruses (Ads) are important human pathogens and valuable gene delivery vehicles. We report here the crystal structure of the species B Ad11 knob complexed with the Ad11-binding region of its receptor CD46. The conformation of bound CD46 differs profoundly from its unbound state, with the bent surface structure straightened into an elongated rod. This mechanism of interaction is likely to be conserved among many pathogens that target CD46 or related molecules. Adenovirus type 11 binding alters the conformation of its receptor CD46.,Persson BD, Reiter DM, Marttila M, Mei YF, Casasnovas JM, Arnberg N, Stehle T Nat Struct Mol Biol. 2007 Feb;14(2):164-6. Epub 2007 Jan 14. PMID:17220899[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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