Structural basis of PP2A inhibition by small t antigen

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of fu...

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Bibliographic Details
Published in:PLoS biology 2007-08, Vol.5 (8), p.e202
Main Authors: Cho, Uhn Soo, Morrone, Seamus, Sablina, Anna A, Arroyo, Jason D, Hahn, William C, Xu, Wenqing
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antigens
Antigens, Viral, Tumor - chemistry
Antigens, Viral, Tumor - genetics
Antigens, Viral, Tumor - metabolism
Binding Sites
Biochemistry
Chemical Biology
Chemistry
Colleges & universities
Crystallography, X-Ray
DNA Mutational Analysis
Humans
In Vitro
Infectious Diseases
Mice
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Phosphatases
Properties
Protein Binding
Protein Conformation
Protein Phosphatase 2 - antagonists & inhibitors
Protein Phosphatase 2 - chemistry
Protein Phosphatase 2 - metabolism
Protein Subunits - antagonists & inhibitors
Protein Subunits - chemistry
Protein Subunits - metabolism
Proteins
Sequence Alignment
Simian virus 40 - immunology
Telomerase
Virology
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Summary:The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of full-length ST in complex with PP2A A subunit at 3.1 A resolution. ST consists of an N-terminal J domain and a C-terminal unique domain that contains two zinc-binding motifs. Both the J domain and second zinc-binding motif interact with the intra-HEAT-repeat loops of HEAT repeats 3-7 of the A subunit, which overlaps with the binding site of the PP2A B56 subunit. Intriguingly, the first zinc-binding motif is in a position that may allow it to directly interact with and inhibit the phosphatase activity of the PP2A catalytic C subunit. These observations provide a structural basis for understanding the oncogenic functions of ST.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.0050202