Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain

被引：18

作者：

Maisonneuve, Pierre ^{[1
,2
]}

Caillet-Saguy, Celia ^{[1
]}

Raynal, Bertrand ^{[3
]}

Gilquin, Bernard ^{[4
]}

Chaffotte, Alain ^{[1
]}

Perez, Javier ^{[5
]}

Zinn-Justin, Sophie ^{[4
]}

Delepierre, Muriel ^{[1
]}

Buc, Henri ^{[6
]}

Cordier, Florence ^{[1
]}

Wolff, Nicolas ^{[1
]}

机构：

[1] Inst Pasteur, Unite Resonance Magnet Nucl Biomol, Dept Biol Struct & Chim, F-75724 Paris 15, France

[2] Univ Paris 06, Cellule Pasteur UPMC, Paris, France

[3] Inst Pasteur, Plate Forme Biophys Macromol, F-75724 Paris 15, France

[4] Saclay, Lab Biol Struct & Radiobiol, Gif Sur Yvette, France

[5] Soleil Synchrotron, Orme Merisiers St Aubin, Gif Sur Yvette, France

[6] Inst Pasteur, F-75724 Paris 15, France

来源：

FEBS JOURNAL | 2014年 / 281卷 / 21期

关键词：

protein tyrosine phosphatase; enzymology; intramolecular regulation; PDZ domain; protein dynamics; PROTEIN-TYROSINE-PHOSPHATASE; MECHANISM; PTPMEG; SYSTEM;

D O I：

10.1111/febs.13024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The human protein tyrosine phosphatase non-receptor type 4 (PTPN4) prevents cells death. Targeting its PDZ domain abrogates this protection and triggers apoptosis. We demonstrate here that the PDZ domain inhibits the phosphatase activity of PTPN4. The mere binding of a PDZ ligand is sufficient to release the catalytic inhibition. We combined analytical ultracentrifugation, small angle X-ray scattering and NMR to understand how the PDZ domain controls PTPN4 activity. We show that the physiologically active PTPN4 two-domain, encompassing the PDZ and the phosphatase domains, adopts a predominant compact conformation in solution. The PDZ ligand binding restores the catalytic competence of PTPN4 disrupting the transient interdomain communication. This study strengthens the emerging notion that PDZ domains can act as regulators of enzyme activity and therefore are active players in the dynamic regulation of signaling pathways.

引用

页码：4852 / 4865

页数：14

共 39 条

[11] Size and Shape of Protein Molecules at the Nanometer Level Determined by Sedimentation, Gel Filtration, and Electron Microscopy [J].