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Esben Meldgaard Høgh Quistgaard

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

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DOI

  • Christian Löw
  • ,
  • Esben M Quistgaard
  • Michael Kovermann
  • ,
  • Madhanagopal Anandapadamanaban
  • ,
  • Jochen Balbach
  • ,
  • Pär Nordlund

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 Tyr307(PP2A-C) or carboxymethylation of Leu309(PP2A-C) abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304(PP2A-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.

Original languageEnglish
JournalBiological Chemistry
Volume395
Issue7-8
Pages (from-to)881-9
Number of pages9
ISSN1431-6730
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

    Research areas

  • Adenosine Triphosphate, Biocatalysis, Humans, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Phosphoprotein Phosphatases, Protein Binding, Protein Conformation, Protein Phosphatase 2, Journal Article, Research Support, Non-U.S. Gov't

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