 |
PDBsum entry 2pkg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase regulator/viral protein
|
PDB id
|
|
|
|
2pkg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural and biochemical insights into the regulation of protein phosphatase 2a by small t antigen of sv40.
|
|
|
Authors
|
|
Y.Chen,
Y.Xu,
Q.Bao,
Y.Xing,
Z.Li,
Z.Lin,
J.B.Stock,
P.D.Jeffrey,
Y.Shi.
|
|
|
Ref.
|
|
Nat Struct Mol Biol, 2007,
14,
527-534.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
