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2bbr

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Revision as of 06:11, 16 May 2018

Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition

Structural highlights

2bbr is a 1 chain structure with sequence from Mcv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2bbz
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Yang JK, Wang L, Zheng L, Wan F, Ahmed M, Lenardo MJ, Wu H. Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition. Mol Cell. 2005 Dec 22;20(6):939-49. PMID:16364918 doi:10.1016/j.molcel.2005.10.023

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bbr"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition==
 <StructureSection load='2bbr' size='340' side='right' caption='[[2bbr]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bbz|2bbz]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bbr OCA], [http://pdbe.org/2bbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bbr RCSB], [http://www.ebi.ac.uk/pdbsum/2bbr PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bbr OCA], [http://pdbe.org/2bbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bbr RCSB], [http://www.ebi.ac.uk/pdbsum/2bbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bbr ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bb/2bbr_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bb/2bbr_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2bbr

From Proteopedia

Revision as of 06:11, 16 May 2018

Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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