Structural and functional elucidation of NF-κB signaling by the p75 neurotrophin receptor through recruitment of TRADD
Zhang, N.; Kisiswa, L.; Ramanujan, A.; Li, Z.; Sim, E. W.; Yuan, W.; Ibanez, C. F.; LIN, Z.
Show abstract
p75 neurotrophin receptor (p75NTR) is a critical mediator of neuronal death and tissue remodeling and has been implicated in various neurodegenerative diseases. The death domain (DD) of p75NTR is an intracellular signaling hub and has been shown to interact with diverse adaptor proteins. However, the structural mechanism and physiological relevance of the adaptor protein TRADD in neuronal p75NTR signaling remain poorly understood. Here we report an NMR structure of the complex between p75NTR-DD and TRADD-DD and elucidate the structural basis of specific DD recognition in the p75NTR/TRADD signaling pathway. Furthermore, we identify spatiotemporal overlap of p75NTR and TRADD expression in developing cerebellar granule neurons (CGNs) at early postnatal stages and reveal the functional role of TRADD recruitment to p75NTR in the regulation of canonical NF-{kappa}B signaling and cell survival in CGNs. Our results provide a new structural framework for understanding how the recruitment of TRADD to p75NTR through DD interactions creates a membrane-proximal platform to propagate downstream signaling in developing neurons.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A subtle structural modification of a synthetic cannabinoid receptor agonist drastically increases its efficacy at the CB1 receptor 95%
- Exifone is a Potent HDAC1 Activator with Neuroprotective Activity in Human Neuronal Models of Neurodegeneration 92%
- Structural Insights into Dopamine Receptor-Ligand Interactions: From Agonists to Antagonists 92%
Similar papers in this journal
- Persulfidation of DJ-1 : Mechanism and Consequences 93%
- Integrating Conformational Dynamics and Perturbation-Based Network Modeling for Mutational Profiling of Binding and Allostery in the SARS-CoV-2 Spike Variant Complexes with Antibodies: Balancing Local and Global Determinants of Mutational Escape Mechanisms 93%
- Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies 93%
Similar papers in this journal
- Cold-induced loss of interaction with HSC70 triggers inflammasome activity of familial cold autoinflammatory syndrome-causing mutants of NLRP3 93%
- Is myeloid-derived growth factor a ligand of the sphingosine-1-phosphate receptor 2? 92%
- Biophysical insight into protein-protein interactions in the Interleukin-11/Interleukin-11Rα/glycoprotein 130 signaling complex 92%
Similar papers in this journal
- Structural Basis of the Transmembrane Domain Dimerization in the Activation Mechanism of TrkA by NGF 95%
- Pharmacologically diverse antidepressant drugs disrupt the interaction of BDNF receptor TRKB and the endocytic adaptor AP-2 93%
- Designing monomeric IFNγ: the significance of domain-swapped dimer structure in IFNγ immune responses 93%
Similar papers in this journal
- Modelling the effects of PPARβδ of innate inflammatory responses in lung tissues 93%
- Identification of a cardiac glycoside exhibiting favorable brain bioavailability and potency for reducing levels of the cellular prion protein 93%
- Interferon-γ as a Potential Inhibitor of SARS-CoV-2 ORF6 Accessory Protein 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.