4pbw

Crystal structure of chicken receptor protein tyrosine phosphatase sigma in complex with TrkC

spinqualitylabelsall models 4pbw, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pbw is a 6 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG Related: 2yd4 Gene: NTRK3, TRKC (CHICK), CRYPalpha1 (CHICK) Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NTRK3_CHICK] Receptor for neurotrophin-3 (NT-3). This is a tyrosine-protein kinase receptor. Known substrates for the trk receptors are SHC1, PI-3 kinase and PLCG1. The KT and KD isoforms fail to stimulate transformation, process outgrowth or survival. Isoform KI25 exhibits tyrosine phosphorylation in the absence of ligand and is unable to mediate survival of neuronal cells. Publication Abstract from PubMed Receptor protein tyrosine phosphatase sigma (RPTPsigma) regulates neuronal extension and acts as a presynaptic nexus for multiple protein and proteoglycan interactions during synaptogenesis. Unknown mechanisms govern the shift in RPTPsigma 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 RPTPsigma extracellular region for interaction with both cis (same cell) and trans (opposite cell) ligands. Crystal structures of RPTPsigma 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 RPTPsigma binding in vitro and disrupt TrkC-dependent synaptic differentiation in neuronal co-culture assays. We propose that transient RPTPsigma ectodomain emergence from the presynaptic proteoglycan layer allows capture by TrkC to form a trans-synaptic complex, the consequent reduction in RPTPsigma flexibility potentiating interactions with additional ligands to orchestrate excitatory synapse formation. Structural basis for extracellular cis and trans RPTPsigma signal competition in synaptogenesis.,Coles CH, Mitakidis N, Zhang P, Elegheert J, Lu W, Stoker AW, Nakagawa T, Craig AM, Jones EY, Aricescu AR Nat Commun. 2014 Nov 11;5:5209. doi: 10.1038/ncomms6209. PMID:25385546 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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