5EYZ

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

5EYZ の概要

• エントリーDOI: 10.2210/pdb5eyz/pdb
• 関連するPDBエントリー: 3NFK 3NFL
• 分子名称: Tyrosine-protein phosphatase non-receptor type 4, CYTO8-RETEV, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: apoptosis, cell death, glioblastoma, multiprotein complexes, pdz domains, peptides design, protein binding, non-receptor type 4, ptpn4, rabies virus, pdz binding motif
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 52951.33

構造登録者

Maisonneuve, P.,Vaney, M.C.,Babault, B.,Caillet-Saguy, C.,Lafon, M.,Delepierre, M.,Cordier, F.,Wolff, N. (登録日: 2015-11-26, 公開日: 2016-06-08, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.09 Å)