2F1S
Crystal Structure of a Viral FLIP MC159
Summary for 2F1S
| Entry DOI | 10.2210/pdb2f1s/pdb |
| Descriptor | Viral CASP8 and FADD-like apoptosis regulator (2 entities in total) |
| Functional Keywords | flip, ded, death receptor signaling, disc, caspase activation, apoptosis |
| Biological source | Molluscum contagiosum virus subtype 1 |
| Total number of polymer chains | 1 |
| Total formula weight | 20794.99 |
| Authors | Li, F.-Y.,Jeffrey, P.D.,Yu, J.W.,Shi, Y. (deposition date: 2005-11-15, release date: 2005-11-29, Last modification date: 2024-02-14) |
| Primary citation | Li, F.-Y.,Jeffrey, P.D.,Yu, J.W.,Shi, Y. Crystal Structure of a Viral FLIP: INSIGHTS INTO FLIP-MEDIATED INHIBITION OF DEATH RECEPTOR SIGNALING. J.Biol.Chem., 281:2960-2968, 2006 Cited by PubMed Abstract: 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. PubMed: 16317000DOI: 10.1074/jbc.M511074200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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