2PKG

Structure of a complex between the A subunit of protein phosphatase 2A and the small t antigen of SV40

Summary for 2PKG

• Entry DOI: 10.2210/pdb2pkg/pdb
• Descriptor: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Small T antigen, ZINC ION (3 entities in total)
• Functional Keywords: protein phosphatase 2a, small t antigen, sv40, regulation, hydrolase regulator-viral protein complex, hydrolase regulator/viral protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (By similarity): P30153; Host cytoplasm: P03081
• Total number of polymer chains: 4
• Total formula weight: 150279.67

Authors

Jeffrey, P.D.,Shi, Y. (deposition date: 2007-04-17, release date: 2007-05-15, Last modification date: 2024-02-21)

Primary citation

Chen, Y.,Xu, Y.,Bao, Q.,Xing, Y.,Li, Z.,Lin, Z.,Stock, J.B.,Jeffrey, P.D.,Shi, Y.
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.
Nat.Struct.Mol.Biol., 14:527-534, 2007

PubMed 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.

PubMed: 17529992
DOI: 10.1038/nsmb1254

Experimental method

X-RAY DIFFRACTION (3.3 Å)