PDBsum entry 1lgq

Go to PDB code: 
protein Protein-protein interface(s) links
Cell cycle PDB id
Jmol PyMol
Protein chains
112 a.a. *
Waters ×144
* Residue conservation analysis
PDB id:
Name: Cell cycle
Title: Crystal structure of the fha domain of the chfr mitotic checkpoint protein
Structure: Cell cycle checkpoint protein chfr. Chain: a, b. Fragment: fha domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.242     R-free:   0.288
Authors: E.S.Stavridi,Y.Huyen,I.R.Loreto,D.M.Scolnick, T.D.Halazonetis,N.P.Pavletich,P.D.Jeffrey
Key ref:
E.S.Stavridi et al. (2002). Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate. Structure, 10, 891-899. PubMed id: 12121644 DOI: 10.1016/S0969-2126(02)00776-1
16-Apr-02     Release date:   08-May-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q96EP1  (CHFR_HUMAN) -  E3 ubiquitin-protein ligase CHFR
664 a.a.
112 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - RING-type E3 ubiquitin transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine


DOI no: 10.1016/S0969-2126(02)00776-1 Structure 10:891-899 (2002)
PubMed id: 12121644  
Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate.
E.S.Stavridi, Y.Huyen, I.R.Loreto, D.M.Scolnick, T.D.Halazonetis, N.P.Pavletich, P.D.Jeffrey.
The Chfr mitotic checkpoint protein is frequently inactivated in human cancer. We determined the three-dimensional structure of its FHA domain in its native form and in complex with tungstate, an analog of phosphate. The structures revealed a beta sandwich fold similar to the previously determined folds of the Rad53 N- and C-terminal FHA domains, except that the Rad53 domains were monomeric, whereas the Chfr FHA domain crystallized as a segment-swapped dimer. The ability of the Chfr FHA domain to recognize tungstate suggests that it shares the ability with other FHA domains to bind phosphoproteins. Nevertheless, differences in the sequence and structure of the Chfr and Rad53 FHA domains suggest that FHA domains can be divided into families with distinct binding properties.
  Selected figure(s)  
Figure 3.
Figure 3. Structure of the Chfr-Tungstate Complex and Comparison to Rad53 FHA Domain-Phosphopeptide Structures(A-D) Comparison of the structures of native Chfr, the Chfr-tungstate complex, and the Rad53 N-FHA and C-FHA domains bound to phosphothreonine (pT)- and phosphotyrosine (pY)-containing peptides, respectively. Backbone of the FHA domains corresponding to boxes A-D, orange; phosphopeptides, light blue; phosphate and tungstate (WO4) groups, red. D+3, aspartic acid three residues C-terminal to the phosphothreonine.(E) Superimposition of the structures of the Chfr-tungstate and Rad53 N-FHA and C-FHA domain-phosphopeptide complexes. FHA domain backbones, gray (various shades); side chains that contact tungstate/phosphate, red (Chfr), green (Rad53 N-FHA), and blue (Rad53 C-FHA); tungstate ion that binds to Chfr, red; phosphothreonine (pT) residue that contacts the Rad53 N-FHA domain, yellow and green; phosphotyrosine (pY) residue that contacts the Rad53 C-FHA domain, yellow and blue.(F) Alignment of Chfr FHA and Rad53 N-FHA and C-FHA domain residues involved in tungstate/phosphate binding. Residues whose side chains are within 3.2 of a tungstate/phosphate oxygen atom, red; residues whose backbone nitrogen (N) contacts a tungstate/phosphate oxygen atom, blue.
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 891-899) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19841063 C.F.Chin, and F.M.Yeong (2010).
Safeguarding entry into mitosis: the antephase checkpoint.
  Mol Cell Biol, 30, 22-32.  
19326084 Y.E.Kwon, Y.S.Kim, Y.M.Oh, and J.H.Seol (2009).
Nuclear localization of Chfr is crucial for its checkpoint function.
  Mol Cells, 27, 359-363.  
19182791 Y.M.Oh, Y.E.Kwon, J.M.Kim, S.J.Bae, B.K.Lee, S.J.Yoo, C.H.Chung, R.J.Deshaies, and J.H.Seol (2009).
Chfr is linked to tumour metastasis through the downregulation of HDAC1.
  Nat Cell Biol, 11, 295-302.  
18253837 H.Kumeta, K.Ogura, S.Adachi, Y.Fujioka, N.Tanuma, K.Tanuma, K.Kikuchi, and F.Inagaki (2008).
The NMR structure of the NIPP1 FHA domain.
  J Biomol NMR, 40, 219-224.
PDB code: 2jpe
  18473721 N.K.Bernstein, F.Karimi-Busheri, A.Rasouli-Nia, R.Mani, G.Dianov, J.N.Glover, and M.Weinfeld (2008).
Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors.
  Anticancer Agents Med Chem, 8, 358-367.  
18656966 X.Liang, and S.R.Van Doren (2008).
Mechanistic insights into phosphoprotein-binding FHA domains.
  Acc Chem Res, 41, 991-999.  
16697215 M.H.Lee, and G.Lozano (2006).
Regulation of the p53-MDM2 pathway by 14-3-3 sigma and other proteins.
  Semin Cancer Biol, 16, 225-234.  
17007879 X.Liang, G.I.Lee, and S.R.Van Doren (2006).
Partially unfolded forms and non-two-state folding of a beta-sandwich: FHA domain from Arabidopsis receptor kinase-associated protein phosphatase.
  J Mol Biol, 364, 225-240.  
15596505 A.Merlino, M.A.Ceruso, L.Vitagliano, and L.Mazzarella (2005).
Open interface and large quaternary structure movements in 3D domain swapped proteins: insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease A.
  Biophys J, 88, 2003-2012.  
16244663 I.J.Byeon, H.Li, H.Song, A.M.Gronenborn, and M.D.Tsai (2005).
Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67.
  Nat Struct Mol Biol, 12, 987-993.
PDB code: 2aff
15674323 M.K.Summers, J.Bothos, and T.D.Halazonetis (2005).
The CHFR mitotic checkpoint protein delays cell cycle progression by excluding Cyclin B1 from the nucleus.
  Oncogene, 24, 2589-2598.  
15793587 X.Yu, K.Minter-Dykhouse, L.Malureanu, W.M.Zhao, D.Zhang, C.J.Merkle, I.M.Ward, H.Saya, G.Fang, J.van Deursen, and J.Chen (2005).
Chfr is required for tumor suppression and Aurora A regulation.
  Nat Genet, 37, 401-406.  
16042389 Z.Ding, G.I.Lee, X.Liang, F.Gallazzi, A.Arunima, and S.R.Van Doren (2005).
PhosphoThr peptide binding globally rigidifies much of the FHA domain from Arabidopsis receptor kinase-associated protein phosphatase.
  Biochemistry, 44, 10119-10134.  
15139812 M.B.Yaffe, and S.J.Smerdon (2004).
The use of in vitro peptide-library screens in the analysis of phosphoserine/threonine-binding domain structure and function.
  Annu Rev Biophys Biomol Struct, 33, 225-244.  
15319434 P.Bieganowski, K.Shilinski, P.N.Tsichlis, and C.Brenner (2004).
Cdc123 and checkpoint forkhead associated with RING proteins control the cell cycle by controlling eIF2gamma abundance.
  J Biol Chem, 279, 44656-44666.  
12582174 E.Alani, J.Y.Lee, M.J.Schofield, A.W.Kijas, P.Hsieh, and W.Yang (2003).
Crystal structure and biochemical analysis of the MutS.ADP.beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair.
  J Biol Chem, 278, 16088-16094.
PDB code: 1nne
12556502 V.I.Bashkirov, E.V.Bashkirova, E.Haghnazari, and W.D.Heyer (2003).
Direct kinase-to-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase.
  Mol Cell Biol, 23, 1441-1452.  
12121642 M.D.Tsai (2002).
FHA: a signal transduction domain with diverse specificity and function.
  Structure, 10, 887-888.  
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.