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| - | [[Image:2f1s.gif|left|200px]] | |
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| - | <!--
| + | ==Crystal Structure of a Viral FLIP MC159== |
| - | The line below this paragraph, containing "STRUCTURE_2f1s", creates the "Structure Box" on the page.
| + | <StructureSection load='2f1s' size='340' side='right'caption='[[2f1s]], [[Resolution|resolution]] 1.40Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <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> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</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=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> |
| - | {{STRUCTURE_2f1s| PDB=2f1s | SCENE= }}
| + | </table> |
| - | | + | == Function == |
| - | '''Crystal Structure of a Viral FLIP MC159'''
| + | [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]] |
| - | ==Overview== | + | Check<jmol> |
| - | 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.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f1/2f1s_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 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].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </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]. |
| - | 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]
| + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __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 Sun May 4 03:21:47 2008''
| + | |
| Structural highlights
Function
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.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature. 1997 Apr 3;386(6624):517-21. PMID:9087414 doi:http://dx.doi.org/10.1038/386517a0
- ↑ Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B, Lenardo MJ, Tomaselli KJ, Cohen JI. Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1172-6. PMID:9037025
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