Startseite Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
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Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A

  • Christian Löw EMAIL logo , Esben M. Quistgaard , Michael Kovermann , Madhanagopal Anandapadamanaban , Jochen Balbach und Pär Nordlund EMAIL logo
Veröffentlicht/Copyright: 8. Juli 2014
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 395 Heft 7-8

Abstract

Protein phosphatase 2A (PP2A) is a highly abundant heterotrimeric Ser/Thr phosphatase involved in the regulation of a variety of signaling pathways. The PP2A phosphatase activator (PTPA) is an ATP-dependent activation chaperone, which plays a key role in the biogenesis of active PP2A. The C-terminal tail of the catalytic subunit of PP2A is highly conserved and can undergo a number of posttranslational modifications that serve to regulate the function of PP2A. Here we have studied structurally the interaction of PTPA with the conserved C-terminal tail of the catalytic subunit carrying different posttranslational modifications. We have identified an additional interaction site for the invariant C-terminal tail of the catalytic subunit on PTPA, which can be modulated via posttranslational modifications. We show that phosphorylation of Tyr307PP2A-C or carboxymethylation of Leu309PP2A-C abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304PP2A-C is of no consequence. We suggest that the invariant C-terminal residues of the catalytic subunit can act as affinity enhancer for different PP2A interaction partners, including PTPA, and a different ‘code’ of posttranslational modifications can favour interactions to one subunit over others.

Keywords: activation chaperone; phosphatase; posttranslational modification; signaling; X-ray structure
Corresponding authors: Christian Löw, Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, S-17177 Stockholm, Sweden; and European Molecular Biology Laboratory, Hamburg Outstation c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany; and Pär Nordlund, Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, S-17177 Stockholm, Sweden; and School of Biological Sciences, Nanyang Technological University, 639798 Singapore, Singapore, e-mail: ,

Acknowledgments

We thank our group members for suggestions and comments on the manuscript. E.M.Q. was supported by The Danish Council for Independent Research (Medical Sciences; grant 271-09-0187). C.L. was supported by a European Molecular Biology Organization (EMBO) postdoctoral fellowship. This research was further supported by grants from the Swedish Research Council, Swedish Cancer Society, as well as a Singapore NRF-CRP (National Research Foundation – Competitive Research Programme) grant. We thank Diamond Light Source for access to beamline I24 (MX5873 and MX6603) that contributed to the results presented here. We acknowledge technical support by the SPC facility at EMBL Hamburg and the Protein Science Facility at the Karolinska Institutet for providing crystallization infrastructure. The research leading to these results has furthermore received funding from the European Community’s Seventh Framework Program (FP7/2007–2013) under BioStruct-X (grant agreement N°783). M.K. and J.B. were supported by the DFG (GRK1026), the BMBF (ProNet-T3), and ERDF by the EU.

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Supplemental Material: The online version of this article (DOI 10.1515/hsz-2014-0106) offers supplementary material, available to authorized users.

Received: 2014-1-20
Accepted: 2014-5-20
Published Online: 2014-7-8
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: conformational transitions in macromolecular interactions
  4. Single-molecule spectroscopy of unfolded proteins and chaperonin action
  5. Influence of the polypeptide environment next to amyloidogenic peptides on fibril formation
  6. Structure of large dsDNA viruses
  7. Functional aspects of extracellular cyclophilins
  8. Generic tools for conditionally altering protein abundance and phenotypes on demand
  9. Structural insights into calmodulin/Munc13 interaction
  10. Interaction of linear polyamines with negatively charged phospholipids: the effect of polyamine charge distance
  11. Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity
  12. Lanthanides as substitutes for calcium ions in the activation of plant α-type phospholipase D
  13. Insights from reconstitution reactions of COPII vesicle formation using pure components and low mechanical perturbation
  14. Identification of key residues in the formate channel FocA that control import and export of formate
  15. Twin-arginine translocation-arresting protein regions contact TatA and TatB
  16. Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
  17. An ancient oxidoreductase making differential use of its cofactors
  18. Biophysical characterization of polyomavirus minor capsid proteins
  19. Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
  20. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
  21. Thermodynamic signatures in macromolecular interactions involving conformational flexibility
https://doi.org/10.1515/hsz-2014-0106
Schlagwörter für diesen Artikel
activation chaperone; phosphatase; posttranslational modification; signaling; X-ray structure

Artikel in diesem Heft

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: conformational transitions in macromolecular interactions
  4. Single-molecule spectroscopy of unfolded proteins and chaperonin action
  5. Influence of the polypeptide environment next to amyloidogenic peptides on fibril formation
  6. Structure of large dsDNA viruses
  7. Functional aspects of extracellular cyclophilins
  8. Generic tools for conditionally altering protein abundance and phenotypes on demand
  9. Structural insights into calmodulin/Munc13 interaction
  10. Interaction of linear polyamines with negatively charged phospholipids: the effect of polyamine charge distance
  11. Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity
  12. Lanthanides as substitutes for calcium ions in the activation of plant α-type phospholipase D
  13. Insights from reconstitution reactions of COPII vesicle formation using pure components and low mechanical perturbation
  14. Identification of key residues in the formate channel FocA that control import and export of formate
  15. Twin-arginine translocation-arresting protein regions contact TatA and TatB
  16. Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
  17. An ancient oxidoreductase making differential use of its cofactors
  18. Biophysical characterization of polyomavirus minor capsid proteins
  19. Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
  20. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
  21. Thermodynamic signatures in macromolecular interactions involving conformational flexibility
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