Article abstract
Nature Structural & Molecular Biology 14, 527 - 534 (2007)
Published online: 27 May 2007 | doi:10.1038/nsmb1254
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40
Yu Chen1,2, Yanhui Xu1,2, Qing Bao1, Yongna Xing1, Zhu Li1, Zheng Lin1, Jeffry B Stock1, Philip D Jeffrey1 & Yigong Shi1
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.
- Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.
- These authors contributed equally to this work.
Correspondence to: Yigong Shi1 e-mail: ygshi@princeton.edu
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