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

• Main Authors: Löw, Christian, Quistgaard, Esben M., Kovermann, Michael, Anandapadamanaban, Madhanagopal, Balbach, Jochen, Nordlund, Pär
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Biological sciences::Biochemistry
• Online Access: https://hdl.handle.net/10356/106914; http://hdl.handle.net/10220/25197
• Institution: Nanyang Technological University

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.