Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40

Y Chen, Y Xu, Q Bao, Y Xing, Z Li, Z Lin… - Nature structural & …, 2007 - nature.com
Y Chen, Y Xu, Q Bao, Y Xing, Z Li, Z Lin, JB Stock, PD Jeffrey, Y Shi
Nature structural & molecular biology, 2007nature.com
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 …
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.
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