title: Structural characterization of the self-association of the death domain of p75(NTR.).
abstract: The neurotrophin receptor p75(NTR) conveys multiple signals via its intracellular death domain. However, how the death domain is activated and interacts with downstream adaptors remains unclear. Here, we report two crystal structures of the p75(NTR) death domain in the form of a non-covalent asymmetric dimer and a Cys379-Cys379 disulfide bond linked symmetric dimer, respectively. These two dimer arrangements have not previously been observed in other death domain-containing proteins. Further analysis shows that both the Cys379-Cys379 disulfide linked and non-covalent full-length p75(NTR) dimers are present on the cell surface. These observations suggest that various oligomers may exist simultaneously on the cell surface, and that p75(NTR) activation and signalling may be modulated by neurotrophins or other factors via inducing a shift of the equilibrium between different oligomeric states.
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Qu
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Gui
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D007368:Interferometry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020349:Surface Plasmon Resonance
chemical_list: D004220:Disulfides; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; C068313:Ngfr protein, rat; D003545:Cysteine