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| | ==Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)== | | ==Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)== |
| - | <StructureSection load='3l89' size='340' side='right' caption='[[3l89]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='3l89' size='340' side='right'caption='[[3l89]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l89]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] 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> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o39|2o39]], [[1ckl|1ckl]], [[3l88|3l88]]</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='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 HUMAN])</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> |
| - | <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://pdbe.org/3l89 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l89 RCSB], [http://www.ebi.ac.uk/pdbsum/3l89 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l89 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == 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 == | | == 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> | + | [https://www.uniprot.org/uniprot/Q2KS96_9ADEN Q2KS96_9ADEN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[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]]
| + | |
| Structural highlights
Function
Q2KS96_9ADEN
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
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cupelli K, Muller S, Persson BD, Jost M, Arnberg N, Stehle T. Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses. J Virol. 2010 Apr;84(7):3189-200. Epub 2010 Jan 13. PMID:20071571 doi:10.1128/JVI.01964-09
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