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

被引：71

作者：

Chen, Yu ^{[1
]}

Xu, Yanhui ^{[1
]}

Bao, Qing ^{[1
]}

Xing, Yongna ^{[1
]}

Li, Zhu ^{[1
]}

Lin, Zheng ^{[1
]}

Stock, Jeffry B. ^{[1
]}

Jeffrey, Philip D. ^{[1
]}

Shi, Yigong ^{[1
]}

机构：

[1] Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2007年 / 14卷 / 06期

关键词：

D O I：

10.1038/nsmb1254

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：527 / 534

页数：8

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