在神经退行性疾病、神经损伤以及恶性黑色素瘤、乳腺癌等特定癌细胞中，神经营养素受体p75NTR的表达水平高度上调。作为一种跨膜受体，p75NTR在神经细胞的功能障碍及死亡过程中起着重要作用；而在恶性黑色素瘤、乳腺癌等特定癌细胞中，它又主要参与了癌细胞的抗凋亡。p75NTR能介导多种信号传导通路，包括NF-κB和细胞死亡通路等，但在不同细胞中其介导的信号传导机制还并不完全清楚。在本项目中，我们以核磁共振为主要技术，同时结合生物物理学、生物化学、细胞生物学等多学科交叉技术，以p75NTR穿膜结构域、近膜结构域以及死亡结构域为对象，研究它们和相应分子在细胞内外的相互作用，并在原子水平阐明各个结构域在p75NTR信号传导中的功能和结构机理，为研发新药物治疗上述疾病提供理论和结构学依据。

In neurodegenerative disease and a variety of nerve insults as well as some specific cancer cells including melanoma and breast cancer cells, p75 neurotrophin receptor (p75NTR) becomes highly upregulated. As a transmembrane receptor, p75NTR plays a crucial role in nerve cell death and dysfunction, while it contributes to the antiapoptosis of melanoma and breast cancer cells. p75NTR can mediate multiple signaling pathways, including NF-κB, cell death and so on. However, the mechanisms of p75NTR-mediated signal transduction in different cells are not fully understood. In this proposal, we will study the transmembrane domain, the juxtamembrane domain and the death domain of p75NTR and their interactions with binding partners inside and outside cells; elucidate the functions of each domain; and reveal the structural mechanisms of p75NTR-mediated signaling at the atomic level using nuclear magnetic resonance as main technique in combination with multidisciplinary cross-technology such as biophysics, biochemistry, cell biology and so on. The deliverables achieved by this research will be the theoretical and structural basis for the future development of novel therapies for the diseases mentioned above.