Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40
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DOI：
10.1038/nsmb1254
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发表时间：
2007-06-01
影响因子：
16.8
通讯作者：
Shi, Yigong
中科院分区：
文献类型：
--
作者：
Chen, Yu;Xu, Yanhui;Shi, Yigong
DNA肿瘤病毒SV 40的小t抗原（ST）通过不明确的机制破坏蛋白磷酸酶2A（PP 2A）的功能来促进细胞转化。与人PP 2A的支架亚基结合的SV 40 ST的核心结构域的晶体结构揭示了ST核心结构域具有新的锌结合折叠并与HEAT重复序列3 - 6的保守脊相互作用，其与B'（也称为PR 61或B56）调节亚基的结合位点重叠。ST对PP 2A核心酶的结合亲和力低于B'。因此，ST在体外不能有效地从PP 2 A全酶中置换B'。值得注意的是，ST通过其N-末端J结构域抑制PP 2A磷酸酶活性。这些研究结果表明，ST可能主要通过抑制PP 2A核心酶的磷酸酶活性发挥作用，并在较小程度上通过调节PP 2A全酶的组装。
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.