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


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.

Top
  1. Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.
  2. These authors contributed equally to this work.

Correspondence to: Yigong Shi1 e-mail: ygshi@princeton.edu



MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.


Extra navigation

Subscribe to Nature Structural & Molecular Biology

Subscribe

Open Innovation Challenges

naturejobs

natureproducts


ADVERTISEMENT