3inb

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{{STRUCTURE_3inb| PDB=3inb | SCENE= }}
 
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===Structure of the measles virus hemagglutinin bound to the CD46 receptor===
 
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{{ABSTRACT_PUBMED_20010840}}
 
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==Disease==
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==Structure of the measles virus hemagglutinin bound to the CD46 receptor==
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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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<StructureSection load='3inb' size='340' side='right'caption='[[3inb]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3inb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Measles_virus_strain_Edmonston Measles virus strain Edmonston]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3INB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3INB FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
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<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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3inb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3inb OCA], [https://pdbe.org/3inb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3inb RCSB], [https://www.ebi.ac.uk/pdbsum/3inb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3inb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HEMA_MEASE HEMA_MEASE] Attaches the virus to cell receptors and thereby initiating infection. Binding of H protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion. May use human CD46 and/or SLAMF1 as receptors for viral entry into the cell. The high degree of interaction between H and MCP/CD46 results in down-regulation of the latter from the surface of infected cells, rendering them more sensitive to c3b-mediated complement lysis.<ref>PMID:9811778</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/in/3inb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=3inb 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 highly contagious measles virus infects millions of individuals worldwide, causing serious disease in children of developing countries. Infection is initiated by attachment of the measles virus hemagglutinin (MV-H), a glycoprotein anchored to the virus envelope, to the host cell receptors CD46 or signaling lymphocyte activation molecule (SLAM). Here we report the crystal structure of MV-H in complex with a CD46 protein spanning the two N-terminal domains. A unique groove at the side of the MV-H beta-propeller domain, which is absent in homologous paramyxovirus attachment proteins, engages residues in both CD46 domains. Key contacts involve a protruding loop in the N-terminal CD46 domain that carries two sequential proline residues (PP motif) and penetrates deeply into a hydrophobic socket in MV-H. We identify a similar PP motif in SLAM, defining a common measles virus recognition epitope in the CD46 and SLAM receptor proteins.
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==Function==
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Structure of the measles virus hemagglutinin bound to the CD46 receptor.,Santiago C, Celma ML, Stehle T, Casasnovas JM Nat Struct Mol Biol. 2010 Jan;17(1):124-9. Epub 2009 Dec 13. PMID:20010840<ref>PMID:20010840</ref>
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[[http://www.uniprot.org/uniprot/HEMA_MEASE HEMA_MEASE]] Attaches the virus to cell receptors and thereby initiating infection. Binding of H protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion. May use human CD46 and/or SLAMF1 as receptors for viral entry into the cell. The high degree of interaction between H and MCP/CD46 results in down-regulation of the latter from the surface of infected cells, rendering them more sensitive to c3b-mediated complement lysis.<ref>PMID:9811778</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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3inb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Measles_virus_strain_edmonston Measles virus strain edmonston]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3INB OCA].
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</div>
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<div class="pdbe-citations 3inb" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Hemagglutinin|Hemagglutinin]]
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*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020010840</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Measles virus strain edmonston]]
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[[Category: Large Structures]]
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[[Category: Casasnovas, J M.]]
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[[Category: Measles virus strain Edmonston]]
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[[Category: Celma, M L.]]
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[[Category: Casasnovas JM]]
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[[Category: Santiago, C.]]
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[[Category: Celma ML]]
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[[Category: Stehle, T.]]
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[[Category: Santiago C]]
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[[Category: Beta propeller]]
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[[Category: Stehle T]]
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[[Category: Cd46]]
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[[Category: Cell membrane]]
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[[Category: Complement control protein]]
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[[Category: Complement pathway]]
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[[Category: Disease mutation]]
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[[Category: Disulfide bond]]
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[[Category: Envelope protein]]
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[[Category: Fertilization]]
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[[Category: Glycoprotein]]
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[[Category: Hemagglutinin]]
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[[Category: Host-virus interaction]]
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[[Category: Immune response]]
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[[Category: Immune system]]
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[[Category: Immune system complex]]
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[[Category: Innate immunity]]
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[[Category: Mcp]]
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[[Category: Measles]]
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[[Category: Membrane]]
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[[Category: Phosphoprotein]]
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[[Category: Scr]]
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[[Category: Signal-anchor]]
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[[Category: Sushi]]
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[[Category: Transmembrane]]
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[[Category: Viral protein]]
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[[Category: Viral protein-immune system complex]]
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[[Category: Viral protein. membrane cofactor protein]]
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[[Category: Virion]]
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[[Category: Virus receptor complex]]
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Current revision

Structure of the measles virus hemagglutinin bound to the CD46 receptor

PDB ID 3inb

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