PDBsum entry 4pbw

Signaling protein

PDB id: 4pbw

Contents

Protein chains

262 a.a.

193 a.a.

Ligands

NAG

PDB id:

4pbw

Name:

Signaling protein

Title:

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

Structure:

Nt-3 growth factor receptor. Chain: b, a, c. Synonym: neurotrophic tyrosine kinase receptor type 3,trkc tyrosine kinase,trk-c. Engineered: yes. Mutation: yes. Other_details: ig3 domain is not visible in electron density, suggesting that this domain had either been proteolytically cleaved during crystallisation or is disordered..

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Gene: ntrk3, trkc. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s. Gene: crypalpha1.

Resolution:

3.05Å R-factor: 0.227 R-free: 0.240

Authors:

C.H.Coles,N.Mitakidis,P.Zhang,J.Elegheert,W.Lu,A.W.Stoker,T.Nakagawa, A.M.Craig,E.Y.Jones,A.R.Aricescu

Key ref:

C.H.Coles et al. (2014). Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis. Nat Commun, 5, 5209. PubMed id: 25385546 DOI: 10.1038/ncomms6209

Date:

14-Apr-14 Release date: 12-Nov-14

Protein chains

Q91044  (NTRK3_CHICK) -  NT-3 growth factor receptor from Gallus gallus

Seq: 827 a.a.

Struc: 262 a.a.*

Protein chains

F1NWE3  (PTPRS_CHICK) -  Receptor-type tyrosine-protein phosphatase S from Gallus gallus

Seq: 1516 a.a.

Struc: 193 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains B, A, C: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

• Enzyme class 2: Chains D, E, F: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/ncomms6209

Nat Commun 5:5209 (2014)

PubMed id: 25385546

Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis.

C.H.Coles, N.Mitakidis, P.Zhang, J.Elegheert, W.Lu, A.W.Stoker, T.Nakagawa, A.M.Craig, E.Y.Jones, A.R.Aricescu.

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.