PDBsum entry 2pkg

Hydrolase regulator/viral protein

PDB id: 2pkg

Contents

Protein chains

579 a.a. *

80 a.a. *

Metals

_ZN ×4

* Residue conservation analysis

PDB id:

2pkg

Name:

Hydrolase regulator/viral protein

Title:

Structure of a complex between the a subunit of protein phosphatase 2a and the small t antigen of sv40

Structure:

Serine/threonine-protein phosphatase 2a 65 kda regulatory subunit a alpha isoform. Chain: a, b. Synonym: pp2a, subunit a, pr65-alpha isoform, pp2a, subunit a, r1- alpha isoform, medium tumor antigen-associated 61 kda protein. Engineered: yes. Small t antigen. Chain: c, d. Fragment: residues 87-174.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp2r1a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Simian virus 40. Organism_taxid: 10633.

Resolution:

3.30Å R-factor: 0.247 R-free: 0.312

Authors:

P.D.Jeffrey,Y.Shi

Key ref:

Y.Chen et al. (2007). Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nat Struct Mol Biol, 14, 527-534. PubMed id: 17529992 DOI: 10.1038/nsmb1254

Date:

17-Apr-07 Release date: 15-May-07

Protein chains

P30153  (2AAA_HUMAN) -  Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform from Homo sapiens

Seq: 589 a.a.

Struc: 579 a.a.

Protein chains

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

Seq: 174 a.a.

Struc: 80 a.a.

DOI no: 10.1038/nsmb1254

Nat Struct Mol Biol 14:527-534 (2007)

PubMed id: 17529992

Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.

Y.Chen, Y.Xu, Q.Bao, Y.Xing, Z.Li, Z.Lin, J.B.Stock, P.D.Jeffrey, Y.Shi.

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.

Selected figure(s)

Figure 2.
Figure 2. Structural features of the core domain of ST. (a) Sequence alignment of ST from SV40 and ST and MT from polyomavirus. Yellow, conserved residues; red, zinc-binding residues; blue squares and magenta triangles, residues that interact with the A subunit of PP2A through hydrogen bonds and van der Waals contacts, respectively; purple asterisks, residues whose mutation abrogates interaction with the A subunit^18, ^35. (b) Superposition showing structural similarity between zinc-binding motifs 1 and 2 in ST (colored yellow and orange, respectively).

Figure 3.
Figure 3. Recognition of the A subunit of PP2A by ST. (a) Close-up view of core domain of ST bound to HEAT repeats 3–6 of the A subunit of PP2A, colored as in Figure 1. (b) Stereo view of ST-A interactions. Orange sticks, side chains; red dotted lines, hydrogen bonds. (c) Almost all the interface residues in the A subunit of PP2A map to the conserved ridge region of HEAT repeats 4–6.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2007, 14, 527-534) copyright 2007.

Figures were selected by an automated process.