5EYZ

CRYSTAL STRUCTURE OF THE PTPN4 PDZ DOMAIN COMPLEXED WITH THE TAILORED PEPTIDE CYTO8-RETEV

Summary for 5EYZ

• Entry DOI: 10.2210/pdb5eyz/pdb
• Related: 3NFK 3NFL
• Descriptor: Tyrosine-protein phosphatase non-receptor type 4, CYTO8-RETEV, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: apoptosis, cell death, glioblastoma, multiprotein complexes, pdz domains, peptides design, protein binding, non-receptor type 4, ptpn4, rabies virus, pdz binding motif
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 52951.33

Authors

Maisonneuve, P.,Vaney, M.C.,Babault, B.,Caillet-Saguy, C.,Lafon, M.,Delepierre, M.,Cordier, F.,Wolff, N. (deposition date: 2015-11-26, release date: 2016-06-08, Last modification date: 2024-10-16)

Primary citation

Maisonneuve, P.,Caillet-Saguy, C.,Vaney, M.C.,Bibi-Zainab, E.,Sawyer, K.,Raynal, B.,Haouz, A.,Delepierre, M.,Lafon, M.,Cordier, F.,Wolff, N.
Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38 gamma.
J.Biol.Chem., 291:16699-16708, 2016

PubMed Abstract: The human protein tyrosine phosphatase non-receptor type 4 (PTPN4) prevents cell death induction in neuroblastoma and glioblastoma cell lines in a PDZ·PDZ binding motifs-dependent manner, but the cellular partners of PTPN4 involved in cell protection are unknown. Here, we described the mitogen-activated protein kinase p38γ as a cellular partner of PTPN4. The main contribution to the p38γ·PTPN4 complex formation is the tight interaction between the C terminus of p38γ and the PDZ domain of PTPN4. We solved the crystal structure of the PDZ domain of PTPN4 bound to the p38γ C terminus. We identified the molecular basis of recognition of the C-terminal sequence of p38γ that displays the highest affinity among all endogenous partners of PTPN4. We showed that the p38γ C terminus is also an efficient inducer of cell death after its intracellular delivery. In addition to recruiting the kinase, the binding of the C-terminal sequence of p38γ to PTPN4 abolishes the catalytic autoinhibition of PTPN4 and thus activates the phosphatase, which can efficiently dephosphorylate the activation loop of p38γ. We presume that the p38γ·PTPN4 interaction promotes cellular signaling, preventing cell death induction.

PubMed: 27246854
DOI: 10.1074/jbc.M115.707208

Experimental method

X-RAY DIFFRACTION (2.09 Å)