title: Death domain complex of the TNFR-1, TRADD, and RIP1 proteins for death-inducing signaling.
abstract: Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor-1 (TNFR-1). TNFR-1-associated death domain (TRADD) protein is an adapter molecule that bridges the interaction between TNFR-1 and receptor-interacting serine/threonine-protein kinase 1 (RIP1). However, the molecular mechanism of the complex formation of these proteins has not yet been identified. Here, the binding among TNFR-1, TRADD, and RIP1 was identified using a GST pull-down assay and Biacore biosensor experiment. This study showed that structural characterization and formation of the death-signaling complex could be predicted using TNFR-1, TRADD, and RIP1. In addition, we found that the structure-based mutations of TNFR-1 (P367A and P368A), TRADD (F266A), and RIP1 (M637A and R638A) disrupted formation of the death domain (DD) complex and prevented stable interactions among those DDs.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Jeong
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea. Electronic address: sbjang@pusan.ac.kr.
authors.forename: Se Bok
authors.initials: SB
authors.lastname: Jang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017209:Apoptosis; D015374:Biosensing Techniques; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055672:Static Electricity; D053199:TNF Receptor-Associated Death Domain Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D053199:TNF Receptor-Associated Death Domain Protein; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: Apoptosis; RIP1; TNFR-1; TRADD