4PBV
Crystal structure of chicken receptor protein tyrosine phosphatase sigma in complex with TrkC
Summary for 4PBV
| Entry DOI | 10.2210/pdb4pbv/pdb |
| Related | 2YD4 |
| Descriptor | NT-3 growth factor receptor, Protein-tyrosine phosphatase CRYPalpha1 isoform, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | signaling protein, synapse cell signalling cell surface receptor |
| Biological source | Gallus gallus (Chicken) More |
| Total number of polymer chains | 5 |
| Total formula weight | 160259.98 |
| Authors | Coles, C.H.,Mitakidis, N.,Zhang, P.,Elegheert, J.,Lu, W.,Stoker, A.W.,Nakagawa, T.,Craig, A.M.,Jones, E.Y.,Aricescu, A.R. (deposition date: 2014-04-14, release date: 2014-11-12, Last modification date: 2024-10-23) |
| Primary citation | Coles, C.H.,Mitakidis, N.,Zhang, P.,Elegheert, J.,Lu, W.,Stoker, A.W.,Nakagawa, T.,Craig, A.M.,Jones, E.Y.,Aricescu, A.R. Structural basis for extracellular cis and trans RPTP sigma signal competition in synaptogenesis. Nat Commun, 5:5209-5209, 2014 Cited by PubMed Abstract: Receptor protein tyrosine phosphatase sigma (RPTPσ) regulates neuronal extension and acts as a presynaptic nexus for multiple protein and proteoglycan interactions during synaptogenesis. Unknown mechanisms govern the shift in RPTPσ function, from outgrowth promotion to synaptic organization. Here, we report crystallographic, electron microscopic and small-angle X-ray scattering analyses, which reveal sufficient inter-domain flexibility in the RPTPσ extracellular region for interaction with both cis (same cell) and trans (opposite cell) ligands. Crystal structures of RPTPσ bound to its postsynaptic ligand TrkC detail an interaction surface partially overlapping the glycosaminoglycan-binding site. Accordingly, heparan sulphate and heparin oligomers compete with TrkC for RPTPσ binding in vitro and disrupt TrkC-dependent synaptic differentiation in neuronal co-culture assays. We propose that transient RPTPσ ectodomain emergence from the presynaptic proteoglycan layer allows capture by TrkC to form a trans-synaptic complex, the consequent reduction in RPTPσ flexibility potentiating interactions with additional ligands to orchestrate excitatory synapse formation. PubMed: 25385546DOI: 10.1038/ncomms6209 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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