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PDBsum entry 2h1l

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protein metals Protein-protein interface(s) links
Viral protein PDB id
2h1l
Jmol
Contents
Protein chains
(+ 6 more) 362 a.a. *
(+ 6 more) 199 a.a. *
Metals
_ZN ×24
* Residue conservation analysis
PDB id:
2h1l
Name: Viral protein
Title: The structure of the oncoprotein sv40 large t antigen and p53 tumor suppressor complex
Structure: Large t antigen. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Fragment: helicase domain, residues 260-627. Engineered: yes. Cellular tumor antigen p53. Chain: m, n, o, p, q, r, s, t, u, v, w, x. Fragment: DNA binding domain, residues 92-292. Synonym: tumor suppressor p53, phosphoprotein p53, antigen ny-co-13.
Source: Simian virus 40. Organism_taxid: 10633. Gene: gene a. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: p53.
Biol. unit: Dodecamer (from PQS)
Resolution:
3.16Å     R-factor:   0.261     R-free:   0.308
Authors: W.Lilyestrom
Key ref: W.Lilyestrom et al. (2006). Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor. Genes Dev, 20, 2373-2382. PubMed id: 16951253
Date:
16-May-06     Release date:   12-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P03070  (LT_SV40) -  Large T antigen
Seq:
Struc:
 
Seq:
Struc:
708 a.a.
362 a.a.*
Protein chains
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
Seq:
Struc:
393 a.a.
199 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     apoptotic process   3 terms 
  Biochemical function     transcription regulatory region DNA binding     4 terms  

 

 
Genes Dev 20:2373-2382 (2006)
PubMed id: 16951253  
 
 
Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor.
W.Lilyestrom, M.G.Klein, R.Zhang, A.Joachimiak, X.S.Chen.
 
  ABSTRACT  
 
The transformation potential of Simian Virus 40 depends on the activities of large T-antigen (LTag), which interacts with several cellular tumor suppressors including the important "guardian" of the genome, p53. Inhibition of p53 function by LTag is necessary for both efficient viral replication and cellular transformation. We determined the crystal structure of LTag in complex with p53. The structure reveals an unexpected hexameric complex of LTag binding six p53 monomers. Structure-guided mutagenesis of LTag and p53 residues supported the p53-LTag interface defined by the complex structure. The structure also shows that LTag binding induces dramatic conformational changes at the DNA-binding area of p53, which is achieved partially through an unusual "methionine switch" within p53. In the complex structure, LTag occupies the whole p53 DNA-binding surface and likely interferes with formation of a functional p53 tetramer. In addition, we showed that p53 inhibited LTag helicase function through direct complex formation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20516128 A.C.Joerger, and A.R.Fersht (2010).
The tumor suppressor p53: from structures to drug discovery.
  Cold Spring Harb Perspect Biol, 2, a000919.  
20100603 B.Xue, R.L.Dunbrack, R.W.Williams, A.K.Dunker, and V.N.Uversky (2010).
PONDR-FIT: a meta-predictor of intrinsically disordered amino acids.
  Biochim Biophys Acta, 1804, 996.  
21209940 D.H.Dube, B.Li, E.J.Greenblatt, S.Nimer, A.K.Raymond, and J.J.Kohler (2010).
A two-hybrid assay to study protein interactions within the secretory pathway.
  PLoS One, 5, e15648.  
20686026 G.Rohaly, K.Korf, S.Dehde, and I.Dornreiter (2010).
Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control.
  J Virol, 84, 10727-10747.  
20219473 I.Cuesta, R.Núñez-Ramírez, S.H.Scheres, D.Gai, X.S.Chen, E.Fanning, and J.M.Carazo (2010).
Conformational rearrangements of SV40 large T antigen during early replication events.
  J Mol Biol, 397, 1276-1286.  
20190820 L.Sauer, D.Gitenay, C.Vo, and V.T.Baron (2010).
Mutant p53 initiates a feedback loop that involves Egr-1/EGF receptor/ERK in prostate cancer cells.
  Oncogene, 29, 2628-2637.  
20023703 M.Morawska-Onyszczuk, K.BieĊ„kowska-Szewczyk, and M.Dobbelstein (2010).
Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction.
  Oncogene, 29, 1773-1786.  
20159469 Y.Chen, R.Dey, and L.Chen (2010).
Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.
  Structure, 18, 246-256.
PDB code: 3kmd
19625393 A.Hermannstädter, C.Ziegler, M.Kühl, W.Deppert, and G.V.Tolstonog (2009).
Wild-type p53 enhances efficiency of simian virus 40 large-T-antigen-induced cellular transformation.
  J Virol, 83, 10106-10118.  
19155208 A.Joubel, R.J.Chalkley, K.F.Medzihradszky, H.Hondermarck, and A.L.Burlingame (2009).
Identification of new p53 acetylation sites in COS-1 cells.
  Mol Cell Proteomics, 8, 1167-1173.  
19553311 D.Ahuja, A.V.Rathi, A.E.Greer, X.S.Chen, and J.M.Pipas (2009).
A structure-guided mutational analysis of simian virus 40 large T antigen: identification of surface residues required for viral replication and transformation.
  J Virol, 83, 8781-8788.  
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.  
19371378 J.Sato, H.Shimizu, T.Kasama, N.Yabuta, and H.Nojima (2009).
GAK, a regulator of clathrin-mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus.
  Genes Cells, 14, 627-641.  
19505650 M.T.Sáenz Robles, and J.M.Pipas (2009).
T antigen transgenic mouse models.
  Semin Cancer Biol, 19, 229-235.  
18410249 A.C.Joerger, and A.R.Fersht (2008).
Structural biology of the tumor suppressor p53.
  Annu Rev Biochem, 77, 557-582.  
18579587 A.Kumar, W.S.Joo, G.Meinke, S.Moine, E.N.Naumova, and P.A.Bullock (2008).
Evidence for a structural relationship between BRCT domains and the helicase domains of the replication initiators encoded by the Polyomaviridae and Papillomaviridae families of DNA tumor viruses.
  J Virol, 82, 8849-8862.  
18186020 C.Chen, C.Huang, S.Chen, J.Liang, W.Lin, G.Ke, H.Zhang, B.Wang, J.Huang, Z.Han, L.Ma, K.Huo, X.Yang, P.Yang, F.He, and T.Tao (2008).
Subunit-subunit interactions in the human 26S proteasome.
  Proteomics, 8, 508-520.  
18092324 C.Heinlein, F.Krepulat, J.Löhler, D.Speidel, W.Deppert, and G.V.Tolstonog (2008).
Mutant p53(R270H) gain of function phenotype in a mouse model for oncogene-induced mammary carcinogenesis.
  Int J Cancer, 122, 1701-1709.  
18366598 C.J.Oldfield, J.Meng, J.Y.Yang, M.Q.Yang, V.N.Uversky, and A.K.Dunker (2008).
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
  BMC Genomics, 9, S1.  
  18778253 G.Chen, L.DenBoer, and J.Shin (2008).
Design of a single plasmid-based modified yeast one-hybrid system for investigation of in vivo protein-protein and protein-DNA interactions.
  Biotechniques, 45, 295-304.  
17401432 A.C.Joerger, and A.R.Fersht (2007).
Structure-function-rescue: the diverse nature of common p53 cancer mutants.
  Oncogene, 26, 2226-2242.  
17986463 B.Ma, and A.J.Levine (2007).
Probing potential binding modes of the p53 tetramer to DNA based on the symmetries encoded in p53 response elements.
  Nucleic Acids Res, 35, 7733-7747.  
17439973 B.Ma, Y.Pan, J.Zheng, A.J.Levine, and R.Nussinov (2007).
Sequence analysis of p53 response-elements suggests multiple binding modes of the p53 tetramer to DNA targets.
  Nucleic Acids Res, 35, 2986-3001.  
17253903 G.Meinke, P.Phelan, S.Moine, E.Bochkareva, A.Bochkarev, P.A.Bullock, and A.Bohm (2007).
The crystal structure of the SV40 T-antigen origin binding domain in complex with DNA.
  PLoS Biol, 5, e23.
PDB codes: 2if9 2ntc
17401423 T.Soussi (2007).
p53 alterations in human cancer: more questions than answers.
  Oncogene, 26, 2145-2156.  
17974914 X.Liu, and R.Marmorstein (2007).
Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.
  Genes Dev, 21, 2711-2716.
PDB code: 2r7g
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 code is shown on the right.