Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain
| Autor: | Alain Chaffotte, Henri Buc, Nicolas Wolff, Javier Pérez, Muriel Delepierre, Bernard Gilquin, Bertrand Raynal, Pierre Maisonneuve, Célia Caillet-Saguy, Sophie Zinn-Justin, Florence Cordier |
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| Přispěvatelé: | Résonance Magnétique Nucléaire des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Biochimie et Biophysique des Macromolécules (Plate-forme), Laboratoire de Biologie Structurale et Radiobiologie (LBSR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Paola Turano, Mario Piccioli, the Bio‐NMR Project (BIO‐NMR‐00170) and the PHC GALILEE 2013 program (28105VF) supported by MAE and MESR are acknowledged for providing access to NMR instrumentation available at CERM (Firenze, Italy). We thank E. Lescop for his technical NMR expertise and helpful discussions (ICSN, Gif/Yvette, France). Financial support from the TGIR‐RMN‐THC Fr3050 CNRS for conducting the research is gratefully acknowledged. PM was supported by grants from the Ministére de l'Enseignement Supérieur et de la Recherche and the Fondation pour la Recherche Médicale (FDT20130927999). CCS is a recipient of a Bourse Roux postdoctoral fellowship from Pasteur Institute., We thank P. England, S. Hoos, V. Bondet, E. Frachon (Proteopole, Institut Pasteur) and C. Simenel (NMR unit of the Institut Pasteur) for their technical expertise., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular MESH: Signal Transduction Protein Conformation intramolecular regulation PDZ Domains Peptide Protein tyrosine phosphatase Ligands protein tyrosine phosphatase Biochemistry 0302 clinical medicine MESH: Structure-Activity Relationship MESH: Protein Conformation X-Ray Diffraction MESH: Nuclear Magnetic Resonance Biomolecular MESH: Ligands MESH: PDZ Domains chemistry.chemical_classification 0303 health sciences MESH: Protein Tyrosine Phosphatase Non-Receptor Type 4/chemistry MESH: Kinetics Protein dynamics MESH: Recombinant Fusion Proteins/chemistry Protein Tyrosine Phosphatase Non-Receptor Type 4 MESH: X-Ray Diffraction Ligand (biochemistry) MESH: Recombinant Fusion Proteins/metabolism Cell biology Solutions protein dynamics Signal transduction MESH: Protein Tyrosine Phosphatase Non-Receptor Type 4/antagonists & inhibitors MESH: Models Molecular Protein Binding Signal Transduction Recombinant Fusion Proteins enzymology Phosphatase PDZ domain Biology MESH: Solutions Catalysis Structure-Activity Relationship 03 medical and health sciences Scattering Small Angle Humans MESH: Protein Binding [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Nuclear Magnetic Resonance Biomolecular Molecular Biology MESH: Scattering Small Angle 030304 developmental biology MESH: Humans MESH: Protein Tyrosine Phosphatase Non-Receptor Type 4/metabolism Cell Biology MESH: Catalysis Peptide Fragments Kinetics Enzyme chemistry sense organs 030217 neurology & neurosurgery MESH: Peptide Fragments/metabolism |
| Zdroj: | FEBS Journal FEBS Journal, Wiley, 2014, 281 (21), pp.4852-4865. ⟨10.1111/febs.13024⟩ FEBS Journal, 2014, 281 (21), pp.4852-4865. ⟨10.1111/febs.13024⟩ |
| ISSN: | 1742-464X 1742-4658 |
| DOI: | 10.1111/febs.13024⟩ |
| Popis: | 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. Structured digital abstract PTPN4_linker-PTP dephosphorylates pTyr peptide by enzymatic study (View interaction) PTPN4_PDZ-PTP dephosphorylates pTyr peptide by enzymatic study (View interaction) |
| Databáze: | OpenAIRE |
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