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Institute of Biophysics has made important progress in the research of complex structure of neurotrophins and their receptors

Author: pagemaker Update time: 2009-09-10

A research paper entitled "Crystal Structure of the Neurotrophin-3 and p75NTR Symmetrical Complex" was published in Nature this July by Professor Tao Jiang's group from the Institute of Biophysics, Chinese Academy of Sciences.  It reported the 2.6 resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75NTR, which provided a novel model for neurotrophins-p75NTR recognition and signal generation.

The neurotrophins (NTs), nerve growth factor(NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. They are also potential drug targets for neural diseases, such as neural injure and Alzheimer?s disease. Previous reports have showed that neurotrophins bind to the extracellular domains of two distinct classes of single-transmembrane cell-surface glycosylated receptors: the p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptors (Trks), which induces either neuronal cell survival or cell apoptosis. While p75NTR binds to all neurotrophins, the Trk subtypes are specific for each neurotrophin. The question of whether neurotrophins stimulate p75NTR by inducing receptor homodimerization is still under debate. Moreover, the mechanisms by which p75NTR and Trk function cooperatively remained elusive.

In this paper, the 2.6 ? resolution 3D structure of neurotrophin-3 in complex with the ectodomain of glycosylated p75NTR was solved by X-ray diffraction technique, and related biochemical experiments were further performed comprehensively. The results have revealed an important molecular mechanism for neurotrophin-receptor recognition and signal transduction, and provided critical structural basis for the design of specific neurotrophins agonists to finely tune neuronal development and treating related neural diseases.

 

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07089.html

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