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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Evidence of complex formation between FADD and c-FLIP death effector domains for the death inducing signaling complex

  • Hwang, Eun Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jeong, Mi Suk (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, So Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jang, Se Bok (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • Received : 2013.11.04
  • Accepted : 2013.12.16
  • Published : 2014.09.30
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Abstract

Adaptor protein FADD forms the death inducing signaling complex (DISC) by recruiting the initiating caspases-8 and -10 through homotypic death effector domain (DED) interactions. Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of death ligand-induced apoptosis downstream of death receptors, and FADD competes with procaspase-8/10 for recruitment for DISC. However, the mechanism of action of FADD and c-FLIP proteins remain poorly understood at the molecular level. In this study, we provide evidence indicating that the death effector domain (DED) of FADD interacts directly with the death effector domain of human c-FLIP. In addition, we use homology modeling to develop a molecular docking model of FADD and c-FLIP proteins. We also find that four structure-based mutants (E80A, L84A, K169A and Y171A) of c-FLIP DEDs disturb the interaction with FADD DED, and that these mutations lower the stability of the c-FLIP DED.

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References

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