Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway.
TRADD is a multifunctional signaling adaptor protein that is recruited to TNFR1 upon ligand binding. The C-terminal of TRADD comprises the "death domain" that is responsible for association of TNFR1 and other death domain-containing proteins such as FADD and RIP. The N-terminal domain (N-TRADD) promotes the recruitment of TRAF2 to ... TNFR1 by binding to the C-terminal of TRAF2, leading to the activation of JNK/AP1 and NF-kappa B. The solution structure of N-TRADD was determined, revealing a novel protein fold. A combination of NMR, BIAcore, and mutagenesis experiments was used to help identify the site of interaction of N-TRADD with C-TRAF2, providing a framework for future attempts to selectively inhibit the TNF signaling pathways.
Mesh Terms:
Amino Acid Sequence, Antigens, CD40, Binding Sites, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Nuclear Magnetic Resonance, Biomolecular, Peptide Fragments, Protein Binding, Protein Structure, Secondary, Proteins, Receptors, Tumor Necrosis Factor, Signal Transduction, Solutions, Surface Plasmon Resonance, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Thermodynamics
Amino Acid Sequence, Antigens, CD40, Binding Sites, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Nuclear Magnetic Resonance, Biomolecular, Peptide Fragments, Protein Binding, Protein Structure, Secondary, Proteins, Receptors, Tumor Necrosis Factor, Signal Transduction, Solutions, Surface Plasmon Resonance, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Thermodynamics
Mol. Cell
Date: Jun. 01, 2000
PubMed ID: 10911999
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