2f1s
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(New page: 200px<br /><applet load="2f1s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f1s, resolution 1.4Å" /> '''Crystal Structure of ...)
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Revision as of 08:11, 21 November 2007
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Crystal Structure of a Viral FLIP MC159
Overview
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.
About this Structure
2F1S is a Single protein structure of sequence from Molluscum contagiosum virus subtype 2. Full crystallographic information is available from OCA.
Reference
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:16317000
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