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[[Image:2f1s.gif|left|200px]]


{{Structure
==Crystal Structure of a Viral FLIP MC159==
|PDB= 2f1s |SIZE=350|CAPTION= <scene name='initialview01'>2f1s</scene>, resolution 1.4&Aring;
<StructureSection load='2f1s' size='340' side='right'caption='[[2f1s]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<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>
|ACTIVITY=
</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>
|GENE=  
<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>
|DOMAIN=
</table>
|RELATEDENTRY=
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f1s OCA], [http://www.ebi.ac.uk/pdbsum/2f1s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f1s RCSB]</span>
[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>
}}
== Evolutionary Conservation ==
 
[[Image:Consurf_key_small.gif|200px|right]]
'''Crystal Structure of a Viral FLIP MC159'''
Check<jmol>
 
  <jmolCheckbox>
 
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f1/2f1s_consurf.spt"</scriptWhenChecked>
==Overview==
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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.
    <text>to colour the structure by Evolutionary Conservation</text>
 
  </jmolCheckbox>
==About this Structure==
</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].
2F1S 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=2F1S OCA].  
<div style="clear:both"></div>
 
== References ==
==Reference==
<references/>
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://www.ncbi.nlm.nih.gov/pubmed/16317000 16317000]
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Molluscum contagiosum virus subtype 1]]
[[Category: Molluscum contagiosum virus subtype 1]]
[[Category: Single protein]]
[[Category: Jeffrey PD]]
[[Category: Jeffrey, P D.]]
[[Category: Li F-Y]]
[[Category: Li, F Y.]]
[[Category: Shi Y]]
[[Category: Shi, Y.]]
[[Category: Yu JW]]
[[Category: Yu, J W.]]
[[Category: caspase activation]]
[[Category: death receptor signaling]]
[[Category: ded]]
[[Category: disc]]
[[Category: flip]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:56:44 2008''

Latest revision as of 09:20, 14 February 2024

Crystal Structure of a Viral FLIP MC159

2f1s, resolution 1.40Å

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