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.

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