Death domain complex of the TNFR-1, TRADD, and RIP1 proteins for death-inducing signaling

Young-Hoon Park; Mi Suk Jeong; Se Bok Jang

doi:10.1016/j.bbrc.2013.12.068

Death domain complex of the TNFR-1, TRADD, and RIP1 proteins for death-inducing signaling

Biochem Biophys Res Commun. 2014 Jan 24;443(4):1155-61. doi: 10.1016/j.bbrc.2013.12.068. Epub 2013 Dec 19.

Authors

Young-Hoon Park¹, Mi Suk Jeong¹, Se Bok Jang²

Affiliations

¹ Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea.
² Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea. Electronic address: [email protected].

PMID: 24361886
DOI: 10.1016/j.bbrc.2013.12.068

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.

Keywords: Apoptosis; RIP1; TNFR-1; TRADD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amino Acid Substitution
Apoptosis
Biosensing Techniques
Humans
Kinetics
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes / chemistry
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism
Mutagenesis, Site-Directed
Protein Binding
Protein Interaction Domains and Motifs
Receptor-Interacting Protein Serine-Threonine Kinases / chemistry*
Receptor-Interacting Protein Serine-Threonine Kinases / genetics
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
Receptors, Tumor Necrosis Factor, Type I / chemistry*
Receptors, Tumor Necrosis Factor, Type I / genetics
Receptors, Tumor Necrosis Factor, Type I / metabolism
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Signal Transduction
Static Electricity
TNF Receptor-Associated Death Domain Protein / chemistry*
TNF Receptor-Associated Death Domain Protein / genetics
TNF Receptor-Associated Death Domain Protein / metabolism

Substances

Multiprotein Complexes
Receptors, Tumor Necrosis Factor, Type I
Recombinant Fusion Proteins
TNF Receptor-Associated Death Domain Protein
RIPK1 protein, human
Receptor-Interacting Protein Serine-Threonine Kinases