%0 Journal Article
%T Structural Basis of PP2A Inhibition by Small t Antigen
%A Uhn Soo Cho
%A Seamus Morrone
%A Anna A. Sablina
%A Jason D. Arroyo
%A William C. Hahn
%A Wenqing Xu
%J PLOS Biology
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pbio.0050202
%X 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 £¿ 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¨C7 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.
%U http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0050202