title: Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A.
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 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Löw
authors.forename: Esben M
authors.initials: EM
authors.lastname: Quistgaard
authors.forename: Michael
authors.initials: M
authors.lastname: Kovermann
authors.forename: Madhanagopal
authors.initials: M
authors.lastname: Anandapadamanaban
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054648:Protein Phosphatase 2 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C087440:PTPA protein, human