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

Yu Chen, Yanhui Xu, Qing Bao, Yongna Xing, Zhu Li, Zheng Lin, Jeffry B. Stock, Philip D. Jeffrey, Yigong Shi

Research output: Contribution to journalArticle

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalNature Structural and Molecular Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2007

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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