skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40

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.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930678
Report Number(s):
BNL-81193-2008-JA
TRN: US200901%%178
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Structural and Molecular Biology; Journal Volume: 14; Journal Issue: 6
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; AFFINITY; ANTIGENS; CRYSTAL STRUCTURE; DNA; IN VITRO; NEOPLASMS; PHOSPHATASES; PROTEINS; REGULATIONS; TRANSFORMATIONS; national synchrotron light source

Citation Formats

Chen,Y., Xu, Y., Bao, Q., Xing, Y., Li, Z., Lin, Z., Stock, J., Jeffrey, P., and Shi, Y.. Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40. United States: N. p., 2007. Web. doi:10.1038/nsmb1254.
Chen,Y., Xu, Y., Bao, Q., Xing, Y., Li, Z., Lin, Z., Stock, J., Jeffrey, P., & Shi, Y.. Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40. United States. doi:10.1038/nsmb1254.
Chen,Y., Xu, Y., Bao, Q., Xing, Y., Li, Z., Lin, Z., Stock, J., Jeffrey, P., and Shi, Y.. Mon . "Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40". United States. doi:10.1038/nsmb1254.
@article{osti_930678,
title = {Structural and Biochemical Insights into the Regulation of Protein Phosphatase 2A by Small t Antigen of SV40},
author = {Chen,Y. and Xu, Y. and Bao, Q. and Xing, Y. and Li, Z. and Lin, Z. and Stock, J. and Jeffrey, P. and Shi, Y.},
abstractNote = {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.},
doi = {10.1038/nsmb1254},
journal = {Nature Structural and Molecular Biology},
number = 6,
volume = 14,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}