2f1s
From Proteopedia
(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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| - | [[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size=" | + | [[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2f1s, resolution 1.4Å" /> | caption="2f1s, resolution 1.4Å" /> | ||
'''Crystal Structure of a Viral FLIP MC159'''<br /> | '''Crystal Structure of a Viral FLIP MC159'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Death receptor signaling is initiated by the assembly of the | + | 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== | ==About this Structure== | ||
| - | 2F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http:// | + | 2F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Molluscum contagiosum virus subtype 2]] | [[Category: Molluscum contagiosum virus subtype 2]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Jeffrey, P | + | [[Category: Jeffrey, P D.]] |
| - | [[Category: Li, F | + | [[Category: Li, F Y.]] |
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: Yu, J | + | [[Category: Yu, J W.]] |
[[Category: caspase activation]] | [[Category: caspase activation]] | ||
[[Category: death receptor signaling]] | [[Category: death receptor signaling]] | ||
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[[Category: flip]] | [[Category: flip]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:48 2008'' |
Revision as of 15:16, 21 February 2008
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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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