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PDBsum entry 2pkg

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protein metals Protein-protein interface(s) links
Hydrolase regulator/viral protein PDB id
2pkg
Jmol
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.
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P30153  (2AAA_HUMAN) -  Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Seq:
Struc:
 
Seq:
Struc:
589 a.a.
579 a.a.
Protein chains
Pfam   ArchSchema ?
P03081  (ST_SV40) -  Small t antigen
Seq:
Struc:
174 a.a.
80 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   9 terms 
  Biological process     positive regulation of extrinsic apoptotic signaling pathway in absence of ligand   27 terms 
  Biochemical function     antigen binding     5 terms  

 

 
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20485545 B.Bollag, C.A.Hofstetter, M.M.Reviriego-Mendoza, and R.J.Frisque (2010).
JC virus small T antigen binds phosphatase PP2A and Rb family proteins and is required for efficient viral DNA replication activity.
  PLoS One, 5, e10606.  
20147387 Q.Meng, S.R.Hagemeier, C.V.Kuny, R.F.Kalejta, and S.C.Kenney (2010).
Simian virus 40 T/t antigens and lamin A/C small interfering RNA rescue the phenotype of an Epstein-Barr virus protein kinase (BGLF4) mutant.
  J Virol, 84, 4524-4533.  
19022468 B.S.Schaffhausen, and T.M.Roberts (2009).
Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer.
  Virology, 384, 304-316.  
19750005 H.G.Chen, W.J.Han, M.Deng, J.Qin, D.Yuan, J.P.Liu, L.Xiao, L.Gong, S.Liang, J.Zhang, Y.Liu, and D.W.Li (2009).
Transcriptional regulation of PP2A-A alpha is mediated by multiple factors including AP-2alpha, CREB, ETS-1, and SP-1.
  PLoS One, 4, e7019.  
19505649 J.Cheng, J.A.DeCaprio, M.M.Fluck, and B.S.Schaffhausen (2009).
Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.
  Semin Cancer Biol, 19, 218-228.  
19721090 M.M.Fluck, and B.S.Schaffhausen (2009).
Lessons in signaling and tumorigenesis from polyomavirus middle T antigen.
  Microbiol Mol Biol Rev, 73, 542.  
19277525 Y.Shi (2009).
Assembly and structure of protein phosphatase 2A.
  Sci China C Life Sci, 52, 135-146.  
19879837 Y.Shi (2009).
Serine/threonine phosphatases: mechanism through structure.
  Cell, 139, 468-484.  
18214640 A.A.Sablina, and W.C.Hahn (2008).
SV40 small T antigen and PP2A phosphatase in cell transformation.
  Cancer Metastasis Rev, 27, 137-146.  
18174170 I.H.Lee, H.J.Lim, S.Yoon, J.K.Seong, D.S.Bae, S.G.Rhee, and Y.S.Bae (2008).
Ahnak protein activates protein kinase C (PKC) through dissociation of the PKC-protein phosphatase 2A complex.
  J Biol Chem, 283, 6312-6320.  
18329957 J.Westermarck, and W.C.Hahn (2008).
Multiple pathways regulated by the tumor suppressor PP2A in transformation.
  Trends Mol Med, 14, 152-160.  
18022798 K.Khalili, I.K.Sariyer, and M.Safak (2008).
Small tumor antigen of polyomaviruses: role in viral life cycle and cell transformation.
  J Cell Physiol, 215, 309-319.  
18663356 S.Kotadia, L.R.Kao, S.A.Comerford, R.T.Jones, R.E.Hammer, and T.L.Megraw (2008).
PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen.
  Oncogene, 27, 6334-6346.  
18291659 V.Janssens, S.Longin, and J.Goris (2008).
PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail).
  Trends Biochem Sci, 33, 113-121.  
18957415 V.R.Ruvolo, S.M.Kurinna, K.B.Karanjeet, T.F.Schuster, A.M.Martelli, J.A.McCubrey, and P.P.Ruvolo (2008).
PKR Regulates B56{alpha}-mediated BCL2 Phosphatase Activity in Acute Lymphoblastic Leukemia-derived REH Cells.
  J Biol Chem, 283, 35474-35485.  
18604448 Y.Liang (2008).
Applications of isothermal titration calorimetry in protein science.
  Acta Biochim Biophys Sin (Shanghai), 40, 565-576.  
18394995 Y.Xing, Z.Li, Y.Chen, J.B.Stock, P.D.Jeffrey, and Y.Shi (2008).
Structural mechanism of demethylation and inactivation of protein phosphatase 2A.
  Cell, 133, 154-163.
PDB codes: 3c5v 3c5w
18922469 Y.Xu, Y.Chen, P.Zhang, P.D.Jeffrey, and Y.Shi (2008).
Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.
  Mol Cell, 31, 873-885.
PDB code: 3dw8
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.