Download MendeleyStructural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.
Chen, Y., Xu, Y., Bao, Q., Xing, Y., Li, Z., Lin, Z., Stock, J.B., Jeffrey, P.D., Shi, Y.(2007) Nat Struct Mol Biol 14: 527-534
- PubMed: 17529992
- DOI: https://doi.org/10.1038/nsmb1254
- PubMed Abstract:
The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular transformation by disrupting the functions of protein phosphatase 2A (PP2A) through a poorly defined mechanism. The crystal structure of the core domain of SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core domain has a novel zinc-binding fold and interacts with the conserved ridge of HEAT repeats 3-6, which overlaps with the binding site for the B' (also called PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its N-terminal J domain. These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes.
Organizational Affiliation:
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.
