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2f1s

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(New page: 200px<br /><applet load="2f1s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f1s, resolution 1.4&Aring;" /> '''Crystal Structure of ...)
Current revision (09:20, 14 February 2024) (edit) (undo)
 
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[[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2f1s, resolution 1.4&Aring;" />
 
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'''Crystal Structure of a Viral FLIP MC159'''<br />
 
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==Overview==
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==Crystal Structure of a Viral FLIP MC159==
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Death receptor signaling is initiated by the assembly of the, death-inducing signaling complex, which culminates in the activation of, the initiator caspase, either caspase-8 or caspase-10. A family of viral, and cellular proteins, known as FLIP, plays an essential role in the, regulation of death receptor signaling. Viral FLIP (v-FLIP) and short, cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death, receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS, remain largely unknown. Here we report a high resolution crystal structure, of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is, a member of the human poxvirus family. Unexpectedly, the two tandem death, effector domains (DEDs) of MC159 rigidly associate with each other through, a hydrophobic interface. Structure-based sequence analysis suggests that, this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between, the two DEDs of MC159 resembles that between the caspase recruitment, domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a, highly conserved binding motif on the surface, to which loss-of-function, mutations in MC159 map. These observations, in conjunction with published, evidence, reveal significant insights into the function of v-FLIP and, suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor, signaling.
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<StructureSection load='2f1s' size='340' side='right'caption='[[2f1s]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2f1s]] 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=2F1S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F1S FirstGlance]. <br>
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2F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA].
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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]] 1.4&#8491;</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=2f1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f1s OCA], [https://pdbe.org/2f1s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f1s RCSB], [https://www.ebi.ac.uk/pdbsum/2f1s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f1s ProSAT]</span></td></tr>
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==Reference==
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</table>
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Crystal structure of a viral FLIP: insights into FLIP-mediated inhibition of death receptor signaling., Li FY, Jeffrey PD, Yu JW, Shi Y, J Biol Chem. 2006 Feb 3;281(5):2960-8. Epub 2005 Nov 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16317000 16317000]
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== Function ==
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[[Category: Molluscum contagiosum virus subtype 2]]
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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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[[Category: Single protein]]
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== Evolutionary Conservation ==
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[[Category: Jeffrey, P.D.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Li, F.Y.]]
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Check<jmol>
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[[Category: Shi, Y.]]
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<jmolCheckbox>
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[[Category: Yu, J.W.]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f1/2f1s_consurf.spt"</scriptWhenChecked>
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[[Category: caspase activation]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: death receptor signaling]]
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<text>to colour the structure by Evolutionary Conservation</text>
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[[Category: ded]]
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</jmolCheckbox>
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[[Category: disc]]
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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=2f1s ConSurf].
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[[Category: flip]]
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<div style="clear:both"></div>
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== References ==
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:18:27 2007''
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Molluscum contagiosum virus subtype 1]]
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[[Category: Jeffrey PD]]
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[[Category: Li F-Y]]
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[[Category: Shi Y]]
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[[Category: Yu JW]]

Current revision

Crystal Structure of a Viral FLIP MC159

PDB ID 2f1s

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