Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jbc.2021.100916
Title: Structural basis of NF-kappa B signaling by the p75 neurotrophin receptor interaction with adaptor protein TRADD through their respective death domains
Authors: Zhang, Ning
Kisiswa, Lilian 
Ramanujan, Ajeena 
Li, Zhen
Sim, Eunice Weiling 
Tian, Xianbin
Yuan, Wensu
Ibanez, Carlos F 
Lin, Zhi 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
NERVE GROWTH-FACTOR
MOLECULAR-CLONING
NMR STRUCTURE
GENE-TRANSFER
EXPRESSION
ASSIGNMENT
P75(NTR)
SYSTEM
VISUALIZATION
RESONANCES
Issue Date: 1-Aug-2021
Publisher: ELSEVIER
Citation: Zhang, Ning, Kisiswa, Lilian, Ramanujan, Ajeena, Li, Zhen, Sim, Eunice Weiling, Tian, Xianbin, Yuan, Wensu, Ibanez, Carlos F, Lin, Zhi (2021-08-01). Structural basis of NF-kappa B signaling by the p75 neurotrophin receptor interaction with adaptor protein TRADD through their respective death domains. JOURNAL OF BIOLOGICAL CHEMISTRY 297 (2). ScholarBank@NUS Repository. https://doi.org/10.1016/j.jbc.2021.100916
Abstract: The p75 neurotrophin receptor (p75NTR) 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 p75NTR 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 p75NTR depends on nerve growth factor and promotes cell survival. However, the structural mechanism and functional significance of TRADD recruitment in neuronal p75NTR signaling remain poorly understood. Here we report an NMR structure of the p75NTR-DD and TRADD-DD complex and reveal the mechanism of specific recognition of the TRADD-DD by the p75NTR-DD mainly through electrostatic interactions. Furthermore, we identified spatiotemporal overlap of p75NTR and TRADD expression in developing cerebellar granule neurons (CGNs) at early postnatal stages and discover the physiological relevance of the interaction between TRADD and p75NTR 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 p75NTR through DD interactions creates a membraneproximal platform, which can be efficiently regulated by various neurotrophic factors through extracellular domains of p75NTR, to propagate downstream signaling in developing neurons.
Source Title: JOURNAL OF BIOLOGICAL CHEMISTRY
URI: https://scholarbank.nus.edu.sg/handle/10635/219097
ISSN: 0021-9258
1083-351X
DOI: 10.1016/j.jbc.2021.100916
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