2bbz
From Proteopedia
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| , resolution 3.8Å | |||||||
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Crystal Structure of MC159 Reveals Molecular Mechanism of DISC Assembly and vFLIP Inhibition
Overview
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.
About this Structure
2BBZ is a Single protein structure of sequence from Molluscum contagiosum virus subtype 2. Full crystallographic information is available from OCA.
Reference
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
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