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

Löw C, Quistgaard EM, Kovermann M, Anandapadamanaban M, Balbach J, Nordlund P

Biol. Chem. 395 (7-8) 881-889 [2014-07-00; online 2014-07-09]

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.

Protein Science Facility (PSF)

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PubMed 25003389

DOI 10.1515/hsz-2014-0106

Crossref 10.1515/hsz-2014-0106


PDB 4NY3 [Human PTPA in complex with peptide]