title: Structural study of the RIPoptosome core reveals a helical assembly for kinase recruitment.
abstract: Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch. RIP1, together with Fas-associated protein with death domain (FADD) and caspase-8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3 to form the necrosome that triggers necroptosis. The RIPoptosome assembles through interactions between the death domains (DDs) of RIP1 and FADD and between death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed the overall structure of the RIP1 DD/FADD DD complex, the core of the RIPoptosome, by negative-stain electron microscopy and modeling. The results show that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas death-inducing signaling complex share a common assembly mechanism. Both complexes adopt a helical conformation that requires type I, II, and III interactions between the death domains.
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry, Yeungnam University , Gyeongsan 712-749, South Korea.
authors.forename: Tae-ho
authors.initials: TH
authors.lastname: Jang
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.forename: Jixi
authors.initials: J
authors.lastname: Li
authors.forename: Claire
authors.initials: C
authors.lastname: Richards
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Hsiao
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D053181:Caspase 8 / Q000737:chemistry* / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry*; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D019014:fas Receptor / Q000737:chemistry
chemical_list: D053200:Fas-Associated Death Domain Protein; D020690:GTPase-Activating Proteins; D046912:Multiprotein Complexes; C490620:Ralbp1 protein, mouse; D019014:fas Receptor; D053181:Caspase 8