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2bbz

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Revision as of 00:25, 10 September 2015

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

Structural highlights

2bbz is a 4 chain structure with sequence from Mcv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2bbr
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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/2bbz"

@@ Line 2: / Line 2: @@
 <StructureSection load='2bbz' size='340' side='right' caption='[[2bbz]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2bbz]] is a 4 chain structure with 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=2BBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BBZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2bbz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mcv1 Mcv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BBZ FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bbr|2bbr]]</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=2bbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bbz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bbz RCSB], [http://www.ebi.ac.uk/pdbsum/2bbz 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=2bbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bbz OCA], [http://pdbe.org/2bbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bbz RCSB], [http://www.ebi.ac.uk/pdbsum/2bbz PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 26: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2bbz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Molluscum contagiosum virus subtype 1]]
+[[Category: Mcv1]]
 [[Category: Ahmed, M]]
 [[Category: Lenardo, M J]]

2bbz

From Proteopedia

Revision as of 00:25, 10 September 2015

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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