4PBX

Crystal structure of the six N-terminal domains of human receptor protein tyrosine phosphatase sigma

Summary for 4PBX

• Entry DOI: 10.2210/pdb4pbx/pdb
• Related: 2YD2 2YD3 2YD9
• Descriptor: Receptor-type tyrosine-protein phosphatase S, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: signaling protein, synapse cell signalling cell surface receptor, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q13332
• Total number of polymer chains: 1
• Total formula weight: 64786.45

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: 2024-10-16)

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

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: 25385546
DOI: 10.1038/ncomms6209

Experimental method

X-RAY DIFFRACTION (3.15 Å)