3BUK
Crystal Structure of the Neurotrophin-3 and p75NTR Symmetrical Complex
Summary for 3BUK
| Entry DOI | 10.2210/pdb3buk/pdb |
| Related | 1NT3 |
| Descriptor | Neurotrophin-3, Tumor necrosis factor receptor superfamily member 16, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | ligand-receptor complex, beta-sheet, neurotrophin-3, p75ntr, cleavage on pair of basic residues, glycoprotein, growth factor, secreted, apoptosis, developmental protein, differentiation, membrane, neurogenesis, transmembrane, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 63860.96 |
| Authors | |
| Primary citation | Gong, Y.,Cao, P.,Yu, H.J.,Jiang, T. Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex. Nature, 454:789-793, 2008 Cited by PubMed Abstract: Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75(NTR)) and tyrosine kinase receptors (Trks). Whereas p75(NTR) binds to all NTs, the Trk subtypes are specific for each NT. The question of whether NTs stimulate p75(NTR) by inducing receptor homodimerization is still under debate. Here we report the 2.6-A resolution crystal structure of neurotrophin-3 (NT-3) complexed to the ectodomain of glycosylated p75(NTR). In contrast to the previously reported asymmetric complex structure, which contains a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR) (ref. 3), we show that NT-3 forms a central homodimer around which two glycosylated p75(NTR) molecules bind symmetrically. Symmetrical binding occurs along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster. A comparison of the symmetrical and asymmetric structures reveals significant differences in ligand-receptor interactions and p75(NTR) conformations. Biochemical experiments indicate that both NT-3 and NGF bind to p75(NTR) with 2:2 stoichiometry in solution, whereas the 2:1 complexes are the result of artificial deglycosylation. We therefore propose that the symmetrical 2:2 complex reflects a native state of p75(NTR) activation at the cell surface. These results provide a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks. PubMed: 18596692DOI: 10.1038/nature07089 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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