PDBsum entry 2pf4

Hydrolase regulator/viral protein

PDB id: 2pf4

Contents

Protein chains

575 a.a. *

163 a.a. *

152 a.a. *

142 a.a. *

Metals

_ZN ×8

* Residue conservation analysis

PDB id:

2pf4

Name:

Hydrolase regulator/viral protein

Title:

Crystal structure of the full-length simian virus 40 small t antigen complexed with the protein phosphatase 2a aalpha subunit

Structure:

Serine/threonine-protein phosphatase 2a 65 kda regulatory subunit a alpha isoform. Chain: a, b, c, d. Synonym: pp2a, subunit a, pr65-alpha isoform, pp2a, subunit a, r1- alpha isoform. Engineered: yes. Small t antigen. Chain: e, f, g, h. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: ppp2r1a. Expressed in: escherichia coli. Expression_system_taxid: 562. Simian virus 40. Organism_taxid: 10633. Strain: va45-54-2.

Resolution:

3.10Å R-factor: 0.247 R-free: 0.304

Authors:

U.Cho,S.Morrone,W.Xu

Key ref:

U.S.Cho et al. (2007). Structural basis of PP2A inhibition by small t antigen. Plos Biol, 5, e202. PubMed id: 17608567

Date:

03-Apr-07 Release date: 07-Aug-07

Protein chains

Q76MZ3  (2AAA_MOUSE) -  Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform from Mus musculus

Seq: 589 a.a.

Struc: 575 a.a.

Protein chain

P03081  (ST_SV40) -  Small t antigen from Simian virus 40

Seq: 174 a.a.

Struc: 163 a.a.*

Protein chain

P03081  (ST_SV40) -  Small t antigen from Simian virus 40

Seq: 174 a.a.

Struc: 152 a.a.*

Protein chains

P03081  (ST_SV40) -  Small t antigen from Simian virus 40

Seq: 174 a.a.

Struc: 142 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Plos Biol 5:e202 (2007)

PubMed id: 17608567

Structural basis of PP2A inhibition by small t antigen.

U.S.Cho, S.Morrone, A.A.Sablina, J.D.Arroyo, W.C.Hahn, W.Xu.

ABSTRACT

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.