2bbr

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[[Image:2bbr.gif|left|200px]]
 
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==Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition==
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The line below this paragraph, containing "STRUCTURE_2bbr", creates the "Structure Box" on the page.
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<StructureSection load='2bbr' size='340' side='right'caption='[[2bbr]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2bbr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_1 Molluscum contagiosum virus subtype 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BBR FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.2&#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=AZI:AZIDE+ION'>AZI</scene></td></tr>
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{{STRUCTURE_2bbr| PDB=2bbr | SCENE= }}
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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=2bbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bbr OCA], [https://pdbe.org/2bbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bbr RCSB], [https://www.ebi.ac.uk/pdbsum/2bbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bbr ProSAT]</span></td></tr>
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</table>
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'''Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition'''
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== Function ==
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[https://www.uniprot.org/uniprot/CFLA_MCV1 CFLA_MCV1] Inhibits TNFRSF1A, TNFRSF6 and TNFRSF12 induced apoptosis. May interfere with caspase-8 recruitment and activation at the death-inducing signaling complex (DISC). May lead to higher virus production and contribute to virus persistence and oncogenicity.<ref>PMID:9087414</ref> <ref>PMID:9037025</ref>
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== Evolutionary Conservation ==
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==Overview==
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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/bb/2bbr_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/main_output.php?pdb_ID=2bbr 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 ==
The death-inducing signaling complex (DISC) comprising Fas, Fas-associated death domain (FADD), and caspase-8/10 is assembled via homotypic associations between death domains (DDs) of Fas and FADD and between death effector domains (DEDs) of FADD and caspase-8/10. Caspase-8/10 and FLICE/caspase-8 inhibitory proteins (FLIPs) that inhibit caspase activation at the DISC level contain tandem DEDs. Here, we report the crystal structure of a viral FLIP, MC159, at 1.2 Angstroms resolution. It reveals a noncanonical fold of DED1, a dumbbell-shaped structure with rigidly associated DEDs and a different mode of interaction in the DD superfamily. Whereas the conserved hydrophobic patch of DED1 interacts with DED2, the corresponding region of DED2 mediates caspase-8 recruitment and contributes to DISC assembly. In contrast, MC159 cooperatively assembles with Fas and FADD via an extensive surface that encompasses the conserved charge triad. This interaction apparently competes with FADD self-association and disrupts higher-order oligomerization required for caspase activation in the DISC.
The death-inducing signaling complex (DISC) comprising Fas, Fas-associated death domain (FADD), and caspase-8/10 is assembled via homotypic associations between death domains (DDs) of Fas and FADD and between death effector domains (DEDs) of FADD and caspase-8/10. Caspase-8/10 and FLICE/caspase-8 inhibitory proteins (FLIPs) that inhibit caspase activation at the DISC level contain tandem DEDs. Here, we report the crystal structure of a viral FLIP, MC159, at 1.2 Angstroms resolution. It reveals a noncanonical fold of DED1, a dumbbell-shaped structure with rigidly associated DEDs and a different mode of interaction in the DD superfamily. Whereas the conserved hydrophobic patch of DED1 interacts with DED2, the corresponding region of DED2 mediates caspase-8 recruitment and contributes to DISC assembly. In contrast, MC159 cooperatively assembles with Fas and FADD via an extensive surface that encompasses the conserved charge triad. This interaction apparently competes with FADD self-association and disrupts higher-order oligomerization required for caspase activation in the DISC.
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==About this Structure==
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Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition.,Yang JK, Wang L, Zheng L, Wan F, Ahmed M, Lenardo MJ, Wu H Mol Cell. 2005 Dec 22;20(6):939-49. PMID:16364918<ref>PMID:16364918</ref>
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2BBR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_1 Molluscum contagiosum virus subtype 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BBR OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition., Yang JK, Wang L, Zheng L, Wan F, Ahmed M, Lenardo MJ, Wu H, Mol Cell. 2005 Dec 22;20(6):939-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16364918 16364918]
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</div>
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<div class="pdbe-citations 2bbr" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Molluscum contagiosum virus subtype 1]]
[[Category: Molluscum contagiosum virus subtype 1]]
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[[Category: Single protein]]
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[[Category: Ahmed M]]
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[[Category: Ahmed, M.]]
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[[Category: Lenardo MJ]]
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[[Category: Lenardo, M J.]]
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[[Category: Wan F]]
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[[Category: Wan, F.]]
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[[Category: Wang L]]
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[[Category: Wang, L.]]
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[[Category: Wu H]]
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[[Category: Wu, H.]]
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[[Category: Yang JK]]
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[[Category: Yang, J K.]]
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[[Category: Zheng L]]
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[[Category: Zheng, L.]]
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[[Category: Virus/viral protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:04:59 2008''
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Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition

PDB ID 2bbr

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