3l89

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{{STRUCTURE_3l89| PDB=3l89 | SCENE= }}
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==Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)==
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===Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)===
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<StructureSection load='3l89' size='340' side='right' caption='[[3l89]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20071571}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3l89]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_adenovirus_21 Human adenovirus 21]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L89 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L89 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o39|2o39]], [[1ckl|1ckl]], [[3l88|3l88]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">32608, L5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=32608 Human adenovirus 21]), 9606, CD46, MCP, MIC10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3l89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l89 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l89 RCSB], [http://www.ebi.ac.uk/pdbsum/3l89 PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l8/3l89_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.
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==Disease==
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Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses.,Cupelli K, Muller S, Persson BD, Jost M, Arnberg N, Stehle T J Virol. 2010 Apr;84(7):3189-200. Epub 2010 Jan 13. PMID:20071571<ref>PMID:20071571</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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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</div>
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== References ==
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==About this Structure==
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<references/>
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[[3l89]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_adenovirus_21 Human adenovirus 21]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L89 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:020071571</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Human adenovirus 21]]
[[Category: Human adenovirus 21]]
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[[Category: Cupelli, K.]]
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[[Category: Cupelli, K]]
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[[Category: Stehle, T.]]
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[[Category: Stehle, T]]
[[Category: Adenovirus]]
[[Category: Adenovirus]]
[[Category: Ccp]]
[[Category: Ccp]]

Revision as of 17:27, 18 December 2014

Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)

3l89, resolution 3.50Å

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