Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jbc.2021.100916
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dc.titleStructural basis of NF-kappa B signaling by the p75 neurotrophin receptor interaction with adaptor protein TRADD through their respective death domains
dc.contributor.authorZhang, Ning
dc.contributor.authorKisiswa, Lilian
dc.contributor.authorRamanujan, Ajeena
dc.contributor.authorLi, Zhen
dc.contributor.authorSim, Eunice Weiling
dc.contributor.authorTian, Xianbin
dc.contributor.authorYuan, Wensu
dc.contributor.authorIbanez, Carlos F
dc.contributor.authorLin, Zhi
dc.date.accessioned2022-04-13T05:00:33Z
dc.date.available2022-04-13T05:00:33Z
dc.date.issued2021-08-01
dc.identifier.citationZhang, 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
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/219097
dc.description.abstractThe 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.
dc.language.isoen
dc.publisherELSEVIER
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectNERVE GROWTH-FACTOR
dc.subjectMOLECULAR-CLONING
dc.subjectNMR STRUCTURE
dc.subjectGENE-TRANSFER
dc.subjectEXPRESSION
dc.subjectASSIGNMENT
dc.subjectP75(NTR)
dc.subjectSYSTEM
dc.subjectVISUALIZATION
dc.subjectRESONANCES
dc.typeArticle
dc.date.updated2022-04-13T03:33:54Z
dc.contributor.departmentPHYSIOLOGY
dc.description.doi10.1016/j.jbc.2021.100916
dc.description.sourcetitleJOURNAL OF BIOLOGICAL CHEMISTRY
dc.description.volume297
dc.description.issue2
dc.published.statePublished
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