7CSQ

Solution structure of the complex between p75NTR-DD and TRADD-DD

Summary for 7CSQ

• Entry DOI: 10.2210/pdb7csq/pdb
• Descriptor: Tumor necrosis factor receptor superfamily member 16, Tumor necrosis factor receptor type 1-associated DEATH domain protein (2 entities in total)
• Functional Keywords: p75 ntr, death domain, tradd, apoptosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 23467.32

Authors

Lin, Z.,Zhang, N. (deposition date: 2020-08-16, release date: 2021-08-25, Last modification date: 2024-05-15)

Primary citation

Zhang, N.,Kisiswa, L.,Ramanujan, A.,Li, Z.,Sim, E.W.,Tian, X.,Yuan, W.,Ibanez, C.F.,Lin, Z.
Structural basis of NF-kappa B signaling by the p75 neurotrophin receptor interaction with adaptor protein TRADD through their respective death domains.
J.Biol.Chem., 297:100916-100916, 2021

PubMed Abstract: The p75 neurotrophin receptor (p75) is a critical mediator of neuronal death and tissue remodeling and has been implicated in various neurodegenerative diseases and cancers. The death domain (DD) of p75 is an intracellular signaling hub and has been shown to interact with diverse adaptor proteins. In breast cancer cells, binding of the adaptor protein TRADD to p75 depends on nerve growth factor and promotes cell survival. However, the structural mechanism and functional significance of TRADD recruitment in neuronal p75 signaling remain poorly understood. Here we report an NMR structure of the p75-DD and TRADD-DD complex and reveal the mechanism of specific recognition of the TRADD-DD by the p75-DD mainly through electrostatic interactions. Furthermore, we identified spatiotemporal overlap of p75 and TRADD expression in developing cerebellar granule neurons (CGNs) at early postnatal stages and discover the physiological relevance of the interaction between TRADD and p75 in the regulation of canonical NF-κB signaling and cell survival in CGNs. Our results provide a new structural framework for understanding how the recruitment of TRADD to p75 through DD interactions creates a membrane-proximal platform, which can be efficiently regulated by various neurotrophic factors through extracellular domains of p75, to propagate downstream signaling in developing neurons.

PubMed: 34175311
DOI: 10.1016/j.jbc.2021.100916

Experimental method

SOLUTION NMR