4PBW

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

4PBW の概要

• エントリーDOI: 10.2210/pdb4pbw/pdb
• 関連するPDBエントリー: 2YD4
• 分子名称: NT-3 growth factor receptor, Protein-tyrosine phosphatase CRYPalpha1 isoform, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: receptor protein tyrosine phosphatase (rptp), synapse cell signalling cell surface receptor, signaling protein
• 由来する生物種: Gallus gallus (Chicken); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 194051.01

構造登録者

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. (登録日: 2014-04-14, 公開日: 2014-11-12, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.05 Å)