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{{STRUCTURE_3l89|  PDB=3l89  |  SCENE=  }}
===Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)===
{{ABSTRACT_PUBMED_20071571}}


==Disease==
==Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)==
[[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>  
<StructureSection load='3l89' size='340' side='right'caption='[[3l89]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3l89]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://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 [https://proteopedia.org/fgij/fg.htm?mol=3L89 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l89 OCA], [https://pdbe.org/3l89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l89 RCSB], [https://www.ebi.ac.uk/pdbsum/3l89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l89 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q2KS96_9ADEN Q2KS96_9ADEN]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l8/3l89_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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/main_output.php?pdb_ID=3l89 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Function==
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>
[[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>  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[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].
</div>
 
<div class="pdbe-citations 3l89" style="background-color:#fffaf0;"></div>
==Reference==
== References ==
<ref group="xtra">PMID:020071571</ref><references group="xtra"/><references/>
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Human adenovirus 21]]
[[Category: Human adenovirus 21]]
[[Category: Cupelli, K.]]
[[Category: Large Structures]]
[[Category: Stehle, T.]]
[[Category: Cupelli K]]
[[Category: Adenovirus]]
[[Category: Stehle T]]
[[Category: Ccp]]
[[Category: Complement control protein]]
[[Category: Complement pathway]]
[[Category: Fiber knob]]
[[Category: Glycoprotein]]
[[Category: Host-virus interaction]]
[[Category: Immune response]]
[[Category: Innate immunity]]
[[Category: Mcp]]
[[Category: Membrane cofactor protein]]
[[Category: Scr]]
[[Category: Short consensus repeat]]
[[Category: Sushi2]]
[[Category: Viral protein]]
[[Category: Viral protein-protein binding complex]]
[[Category: Virus receptor complex]]
Retrieved from "https://proteopedia.org/3l89"