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PDBsum entry 1d5v

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protein links
Gene regulation PDB id
1d5v
Jmol
Contents
Protein chain
94 a.a. *
* Residue conservation analysis
PDB id:
1d5v
Name: Gene regulation
Title: Solution structure of the forkhead domain of the adipocyte- transcription factor freac-11 (s12)
Structure: S12 transcription factor (fkh-14). Chain: a. Fragment: DNA-binding domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: adipose tissue. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 25 models
Authors: M.J.P.Van Dongen,A.Cederberg,P.Carlsson,S.Enerback, M.Wikstrom
Key ref:
M.J.van Dongen et al. (2000). Solution structure and dynamics of the DNA-binding domain of the adipocyte-transcription factor FREAC-11. J Mol Biol, 296, 351-359. PubMed id: 10669593 DOI: 10.1006/jmbi.1999.3476
Date:
12-Oct-99     Release date:   11-Oct-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99958  (FOXC2_HUMAN) -  Forkhead box protein C2
Seq:
Struc:
501 a.a.
94 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     sequence-specific DNA binding transcription factor activity     2 terms  

 

 
DOI no: 10.1006/jmbi.1999.3476 J Mol Biol 296:351-359 (2000)
PubMed id: 10669593  
 
 
Solution structure and dynamics of the DNA-binding domain of the adipocyte-transcription factor FREAC-11.
M.J.van Dongen, A.Cederberg, P.Carlsson, S.Enerbäck, M.Wikström.
 
  ABSTRACT  
 
Transcription factors of the forkhead type share a highly conserved DNA-binding domain of about 100 amino acid residues. FREAC-11, expressed in adipocytes, belongs to this class. Here, we report on NMR studies that established the three-dimensional structure of the FREAC-11, DNA-binding domain. Although apparent similarities to the structures of other members within the forkhead family are observed, the structure also reveals some remarkable differences. Along with the complementary dynamics, the data provide insight into the fundamentals of sequence specificity within a highly conserved motif.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. (a) Side-by-side view of the 25 low-energy NMR structures of FREAC-11 DBD(1-94) in which the backbone atoms in the structured regions (residues 4-65, 77-80) are superimposed. (b) Schematic representation of the FREAC-11-DBD(1-94) structure, highlighting the polar and charged residues protruding from H3. HNCA, HN(CO)CA, HNCACB, CACB-(CO)NH and HNCO experiments were used to obtain sequential assignments for the backbone, whereas the side-chain resonances were assigned using TOCSY-[15N]HSQC (40 ms mixing), C(CO)NH, H(CCO)NH and HC(C)H-TOCSY experiments. Distance information was extracted from NOESY-[15N]HSQC experiments with mixing times of 40, 100 and 200 ms, as well as from two NOESY-[13C]HSQC experiments (120 ms mixing) optimized for aliphatic and aromatic carbon resonances, respectively. An HNHA experiment was recorded to obtain 3J[HN-Ha] coupling constants. Cross-correlation rates (G) between the [13C^a]-[1Ha] dipolar and 13C' chemical shift anisotropy relaxation mechanisms [Yang et al 1998], and between [13C^a]-[1Ha] and [15N]-[1HN] dipolar interactions [Yang and Kay 1998] were derived as described. An H(N)COCG experiment was recorded to assess 3J[C'-Cg] scalar couplings [Konrat et al 1997]. All NMR spectra were acquired on Varian Unity-INOVA spectrometers operating at 500, 600 and 800 MHz, and were carried out at 27 °C. NMR data were processed and analyzed using NMRPipe [Delaglio et al 1995] and ANSIG version 3.3 [Kraulis et al 1994], respectively. Distance restraints were obtained by classifying relative NOE cross peak intensities as strong (1.8-2.7 Å), medium (1.8-3.3 Å), weak (1.8-5.0 Å) and very weak (1.8-8.0 Å). The upper distance limits corresponding to strong and medium strength NOE values were subsequently raised with 0.3 and 0.5 Å for NOEs involving NH and methyl resonances, respectively. Distances involving methyl groups and non-stereospecifically assigned aromatic ring and methylene protons were represented as a (Sr -6)1/6 sums. In addition to the 965 restraints for which unambiguous assignments were available, 77 ambiguous distance restraints were applied. Backbone phi, Greek angles were restrained to -120(±40) ° for residues with 3J[HN-Ha]>8.0 Hz and for residues with DC^a< -1 ppm and DHa>0.2 ppm. In addition, phi, Greek angles were restrained to -65(±25) ° for residues with 3J[HN-Ha]<5.0 Hz and for residues with DC^a >1 ppm and DHa < -0.2 ppm. Backbone q angles were restrained to -40(±30) ° for residues with G[CaHa,C'] > 10 s -1, based on a calculated relationship between q and G[CaHa,C'] [Yang et al 1998]. Side-chain x[1] angles were either restrained to -60(±30) ° for residues with 2.5 Hz<3J[C'-Cg]<5.0 Hz [Hu and Bax 1997], or, alternatively, on the basis of relative NOE intensities involving the two b methylene protons. Distance restraints representing hydrogen bonds were included for residues showing protection from fast amide-hydrogen exchange, as well as dihedral angles and NOE patterns diagnostic of a-helical secondary structure.
Figure 3.
Figure 3. (a) The helical regions in FREAC-11 DBD(1-94), the HNF-3g-DNA complex [Clark et al 1993], free Genesis [Marsden et al 1998] and the Genesis-DNA complex [Jin et al 1999], with backbone atoms of H1 and H2 superimposed. (b) Graphical representations of distance difference matrices [Akke et al 1995] comparing the internal C^a-C^a distances in the ensembles of NMR structures of FREAC-11 DBD(1-94) and Genesis (top) and comparing the ensemble of FREAC-11 DBD(1-94) and the X-ray structure of HNF-3g (bottom). The lower right halves of the matrices show the mean values, while the upper left halves show the RMSD values of the distance differences.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 296, 351-359) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21082705 J.Lin, T.Zhou, and J.Wang (2011).
Solution structure of the human HSPC280 protein.
  Protein Sci, 20, 216-223.
PDB code: 2l2o
21068205 J.Y.Fan, B.Han, J.Qiao, B.L.Liu, Y.R.Ji, S.F.Ge, H.D.Song, and X.Q.Fan (2011).
Functional study on a novel missense mutation of the transcription factor FOXL2 causes blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).
  Mutagenesis, 26, 283-289.  
21416545 Y.P.Chu, C.H.Chang, J.H.Shiu, Y.T.Chang, C.Y.Chen, and W.J.Chuang (2011).
Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping and DNA binding.
  Protein Sci, 20, 908-924.
PDB code: 2kiu
20360045 D.R.Littler, M.Alvarez-Fernández, A.Stein, R.G.Hibbert, T.Heidebrecht, P.Aloy, R.H.Medema, and A.Perrakis (2010).
Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence.
  Nucleic Acids Res, 38, 4527-4538.
PDB code: 3g73
  20664696 M.Ali, B.Buentello-Volante, M.McKibbin, J.A.Rocha-Medina, N.Fernandez-Fuentes, W.Koga-Nakamura, A.Ashiq, K.Khan, A.P.Booth, G.Williams, Y.Raashid, H.Jafri, A.Rice, C.F.Inglehearn, and J.C.Zenteno (2010).
Homozygous FOXE3 mutations cause non-syndromic, bilateral, total sclerocornea, aphakia, microphthalmia and optic disc coloboma.
  Mol Vis, 16, 1162-1168.  
18816404 C.D.Fetterman, B.Rannala, and M.A.Walter (2008).
Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.
  BMC Evol Biol, 8, 261.  
18786403 M.M.Brent, R.Anand, and R.Marmorstein (2008).
Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification.
  Structure, 16, 1407-1416.
PDB codes: 3co6 3co7 3coa
18313957 O.Trott, K.Siggers, B.Rost, and A.G.Palmer (2008).
Protein conformational flexibility prediction using machine learning.
  J Magn Reson, 192, 37-47.  
18391969 T.Obsil, and V.Obsilova (2008).
Structure/function relationships underlying regulation of FOXO transcription factors.
  Oncogene, 27, 2263-2275.  
17244620 E.Boura, J.Silhan, P.Herman, J.Vecer, M.Sulc, J.Teisinger, V.Obsilova, and T.Obsil (2007).
Both the N-terminal loop and wing W2 of the forkhead domain of transcription factor Foxo4 are important for DNA binding.
  J Biol Chem, 282, 8265-8275.  
16407075 J.C.Stroud, Y.Wu, D.L.Bates, A.Han, K.Nowick, S.Paabo, H.Tong, and L.Chen (2006).
Structure of the forkhead domain of FOXP2 bound to DNA.
  Structure, 14, 159-166.
PDB code: 2a07
16624804 K.L.Tsai, C.Y.Huang, C.H.Chang, Y.J.Sun, W.J.Chuang, and C.D.Hsiao (2006).
Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins.
  J Biol Chem, 281, 17400-17409.
PDB code: 2c6y
15656969 B.S.Pohl, and W.Knöchel (2005).
Of Fox and Frogs: Fox (fork head/winged helix) transcription factors in Xenopus development.
  Gene, 344, 21-32.  
15299087 R.A.Saleem, S.Banerjee-Basu, T.C.Murphy, A.Baxevanis, and M.A.Walter (2004).
Essential structural and functional determinants within the forkhead domain of FOXC1.
  Nucleic Acids Res, 32, 4182-4193.  
14997560 S.Banerjee-Basu, and A.D.Baxevanis (2004).
Structural analysis of disease-causing mutations in the P-subfamily of forkhead transcription factors.
  Proteins, 54, 639-647.  
12692134 B.Wang, D.Lin, C.Li, and P.Tucker (2003).
Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors.
  J Biol Chem, 278, 24259-24268.  
14581224 H.Yan, and X.Liao (2003).
Amino acid substitutions in a long flexible sequence influence thermodynamics and internal dynamic properties of winged helix protein genesis and its DNA complex.
  Biophys J, 85, 3248-3254.  
12801727 O.J.Lehmann, J.C.Sowden, P.Carlsson, T.Jordan, and S.S.Bhattacharya (2003).
Fox's in development and disease.
  Trends Genet, 19, 339-344.  
11839303 C.A.Andersen, A.G.Palmer, S.Brunak, and B.Rost (2002).
Continuum secondary structure captures protein flexibility.
  Structure, 10, 175-184.  
11943768 M.K.Dahle, L.M.Grønning, A.Cederberg, H.K.Blomhoff, N.Miura, S.Enerbäck, K.A.Taskén, and K.Taskén (2002).
Mechanisms of FOXC2- and FOXD1-mediated regulation of the RI alpha subunit of cAMP-dependent protein kinase include release of transcriptional repression and activation by protein kinase B alpha and cAMP.
  J Biol Chem, 277, 22902-22908.  
12402362 P.P.Liu, Y.C.Chen, C.Li, Y.H.Hsieh, S.W.Chen, S.H.Chen, W.Y.Jeng, and W.J.Chuang (2002).
Solution structure of the DNA-binding domain of interleukin enhancer binding factor 1 (FOXK1a).
  Proteins, 49, 543-553.
PDB code: 1jxs
11876636 W.Sheng, M.Rance, and X.Liao (2002).
Structure comparison of two conserved HNF-3/fkh proteins HFH-1 and genesis indicates the existence of folding differences in their complexes with a DNA binding sequence.
  Biochemistry, 41, 3286-3293.
PDB code: 1kq8
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.