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PDBsum entry 1n4m
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protein Protein-protein interface(s) links
Cell cycle PDB id
1n4m

 

 

 

 

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Contents
Protein chains
345 a.a. *
18 a.a. *
12 a.a. *
Waters ×261
* Residue conservation analysis
PDB id:
1n4m
Name: Cell cycle
Title: Structure of rb tumor suppressor bound to the transactivation domain of e2f-2
Structure: Retinoblastoma pocket. Chain: a, b. Fragment: residues 380-785. Engineered: yes. Transcription factor e2f2. Chain: c, d, e. Fragment: residues 410-427. Synonym: e2f-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in homo sapiens (human).
Biol. unit: Pentamer (from PQS)
Resolution:
2.20Å     R-factor:   0.222     R-free:   0.282
Authors: C.Lee,J.H.Chang,H.S.Lee,Y.Cho
Key ref: C.Lee et al. (2002). Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor. Genes Dev, 16, 3199-3212. PubMed id: 12502741
Date:
31-Oct-02     Release date:   07-Jan-03    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06400  (RB_HUMAN) -  Retinoblastoma-associated protein from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		928 a.a.
345 a.a.*
Protein chains
Pfam   ArchSchema ?
Q14209  (E2F2_HUMAN) -  Transcription factor E2F2 from Homo sapiens
Seq:
Struc: 		437 a.a.
18 a.a.
Protein chain
Pfam   ArchSchema ?
Q14209  (E2F2_HUMAN) -  Transcription factor E2F2 from Homo sapiens
Seq:
Struc: 		437 a.a.
12 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Genes Dev 16:3199-3212 (2002)
PubMed id: 12502741  
 
 
Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor.
C.Lee, J.H.Chang, H.S.Lee, Y.Cho.
 
  ABSTRACT  
 
Repression of E2F transcription activity by the retinoblastoma (Rb) tumor suppressor through its interaction with the transactivation domain of the E2F transcription factor is one of the central features of G1/S arrest in the mammalian cell cycle. Deregulation of the Rb-E2F interaction results in hyperproliferation, lack of differentiation, and apoptosis, and can lead to cancer. The 2.2-A crystal structure of the Rb pocket complexed with an 18-residue transactivation-domain peptide of E2F-2 reveals that the boomerang-shaped peptide binds to the highly conserved interface between the A-box and the B-box of the Rb pocket in a bipartite manner. The N-terminal segment of the E2F-2 peptide in an extended beta-strand-like structure interacts with helices from the conserved groove at the A-B interface, whereas the C-terminal segment, which contains one 3(10) helix, binds to a groove mainly formed by A-box helices. The flexibility in the middle of the E2F-2 peptide is essential for the tight association of E2F to the Rb pocket. The binding of Rb to the E2F-2 peptide conceals several conserved residues that are crucial for transcription activation of E2F. We provide the structural basis for the Rb-mediated repression of E2F transcription activity without the requirement of histone-modifying enzymes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21491492 E.R.Balog, J.R.Burke, G.L.Hura, and S.M.Rubin (2011).
Crystal structure of the unliganded retinoblastoma protein pocket domain.
  Proteins, 79, 2010-2014.
PDB code: 3pom
21143199 M.J.Cecchini, and F.A.Dick (2011).
The biochemical basis of CDK phosphorylation-independent regulation of E2F1 by the retinoblastoma protein.
  Biochem J, 434, 297-308.  
20871633 R.B.Delston, K.A.Matatall, Y.Sun, M.D.Onken, and J.W.Harbour (2011).
p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis.
  Oncogene, 30, 588-599.  
21399612 Y.C.Kim, S.Y.Kim, J.M.Mellado-Gil, H.Yadav, W.Neidermyer, A.K.Kamaraju, and S.G.Rane (2011).
RB regulates pancreas development by stabilizing Pdx1.
  EMBO J, 30, 1563-1576.  
20088881 L.B.Chemes, I.E.Sánchez, C.Smal, and G.de Prat-Gay (2010).
Targeting mechanism of the retinoblastoma tumor suppressor by a prototypical viral oncoprotein. Structural modularity, intrinsic disorder and phosphorylation of human papillomavirus E7.
  FEBS J, 277, 973-988.  
20861300 P.Acharya, N.Raj, M.S.Buckley, L.Zhang, S.Duperon, G.Williams, R.W.Henry, and D.N.Arnosti (2010).
Paradoxical instability-activity relationship defines a novel regulatory pathway for retinoblastoma proteins.
  Mol Biol Cell, 21, 3890-3901.  
19098921 D.Gerber, S.J.Maerkl, and S.R.Quake (2009).
An in vitro microfluidic approach to generating protein-interaction networks.
  Nat Methods, 6, 71-74.  
19823669 H.Wang, L.B.Carey, Y.Cai, H.Wijnen, and B.Futcher (2009).
Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets.
  PLoS Biol, 7, e1000189.  
19651603 J.C.Ferreon, M.A.Martinez-Yamout, H.J.Dyson, and P.E.Wright (2009).
Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein.
  Proc Natl Acad Sci U S A, 106, 13260-13265.
PDB code: 2kje
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.  
19457859 M.R.Tallack, J.R.Keys, P.O.Humbert, and A.C.Perkins (2009).
EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2.
  J Biol Chem, 284, 20966-20974.  
17967892 M.DeRan, M.Pulvino, E.Greene, C.Su, and J.Zhao (2008).
Transcriptional activation of histone genes requires NPAT-dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition.
  Mol Cell Biol, 28, 435-447.  
17786943 T.Tonini, G.D'Andrilli, A.Fucito, L.Gaspa, and L.Bagella (2008).
Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements.
  J Cell Physiol, 214, 295-300.  
17854503 F.A.Dick (2007).
Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts?
  Cell Div, 2, 26.  
17173068 H.L.Borges, I.C.Hunton, and J.Y.Wang (2007).
Reduction of apoptosis in Rb-deficient embryos via Abl knockout.
  Oncogene, 26, 3868-3877.  
17996702 M.Hassler, S.Singh, W.W.Yue, M.Luczynski, R.Lakbir, F.Sanchez-Sanchez, T.Bader, L.H.Pearl, and S.Mittnacht (2007).
Crystal structure of the retinoblastoma protein N domain provides insight into tumor suppression, ligand interaction, and holoprotein architecture.
  Mol Cell, 28, 371-385.
PDB code: 2qdj
17612494 S.Tyagi, A.L.Chabes, J.Wysocka, and W.Herr (2007).
E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases.
  Mol Cell, 27, 107-119.  
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
17380128 Y.Inoue, M.Kitagawa, and Y.Taya (2007).
Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage.
  EMBO J, 26, 2083-2093.  
17292836 Y.Nakamura, K.Nakano, T.Umehara, M.Kimura, Y.Hayashizaki, A.Tanaka, M.Horikoshi, B.Padmanabhan, and S.Yokoyama (2007).
Structure of the oncoprotein gankyrin in complex with S6 ATPase of the 26S proteasome.
  Structure, 15, 179-189.
PDB codes: 2dvw 2dwz
16936748 A.Felsani, A.M.Mileo, and M.G.Paggi (2006).
Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins.
  Oncogene, 25, 5277-5285.  
16638975 J.W.Harbour (2006).
Eye cancer: unique insights into oncogenesis: the Cogan Lecture.
  Invest Ophthalmol Vis Sci, 47, 1736-1745.  
15806172 A.Ledl, D.Schmidt, and S.Müller (2005).
Viral oncoproteins E1A and E7 and cellular LxCxE proteins repress SUMO modification of the retinoblastoma tumor suppressor.
  Oncogene, 24, 3810-3818.  
15669057 D.X.Nguyen, and D.J.McCance (2005).
Role of the retinoblastoma tumor suppressor protein in cellular differentiation.
  J Cell Biochem, 94, 870-879.  
15986142 R.Halaban (2005).
Rb/E2F: a two-edged sword in the melanocytic system.
  Cancer Metastasis Rev, 24, 339-356.  
16360038 S.M.Rubin, A.L.Gall, N.Zheng, and N.P.Pavletich (2005).
Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release.
  Cell, 123, 1093-1106.
PDB code: 2aze
16279839 V.Neduva, R.Linding, I.Su-Angrand, A.Stark, F.de Masi, T.J.Gibson, J.Lewis, L.Serrano, and R.B.Russell (2005).
Systematic discovery of new recognition peptides mediating protein interaction networks.
  PLoS Biol, 3, e405.  
15545624 P.W.Lewis, E.L.Beall, T.C.Fleischer, D.Georlette, A.J.Link, and M.R.Botchan (2004).
Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex.
  Genes Dev, 18, 2929-2940.  
14527410 F.A.Dick, and N.Dyson (2003).
pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities.
  Mol Cell, 12, 639-649.  
12606716 K.Munger (2003).
Clefts, grooves, and (small) pockets: the structure of the retinoblastoma tumor suppressor in complex with its cellular target E2F unveiled.
  Proc Natl Acad Sci U S A, 100, 2165-2167.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
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.

 

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