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| - | [[Image:2f1s.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2f1s| PDB=2f1s | SCENE= }} | | {{STRUCTURE_2f1s| PDB=2f1s | SCENE= }} |
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| - | '''Crystal Structure of a Viral FLIP MC159'''
| + | ===Crystal Structure of a Viral FLIP MC159=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16317000}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16317000 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16317000}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Disc]] | | [[Category: Disc]] |
| | [[Category: Flip]] | | [[Category: Flip]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:21:47 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:07:55 2008'' |
Revision as of 13:07, 27 July 2008
Template:STRUCTURE 2f1s
Crystal Structure of a Viral FLIP MC159
Template:ABSTRACT PUBMED 16317000
About this Structure
2F1S is a Single protein structure of sequence from Molluscum contagiosum virus subtype 1. 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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