PDBsum entry 1uzc

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protein links
Nuclear protein PDB id
Protein chain
69 a.a. *
* Residue conservation analysis
PDB id:
Name: Nuclear protein
Title: The structure of an ff domain from human hypa/fbp11
Structure: Hypothetical protein flj21157. Chain: a. Fragment: ff domain, residues 250-319. Synonym: huntingtin-interacting protein hypa/fbp11. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 23 models
Authors: M.D.Allen,P.Jemth,A.Friedler,O.Schon,M.Bycroft
Key ref:
M.Allen et al. (2002). The structure of an FF domain from human HYPA/FBP11. J Mol Biol, 323, 411-416. PubMed id: 12381297 DOI: 10.1016/S0022-2836(02)00968-3
09-Mar-04     Release date:   05-Apr-04    
Supersedes: 1h40
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Protein chain
Pfam   ArchSchema ?
O75400  (PR40A_HUMAN) -  Pre-mRNA-processing factor 40 homolog A
957 a.a.
69 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1016/S0022-2836(02)00968-3 J Mol Biol 323:411-416 (2002)
PubMed id: 12381297  
The structure of an FF domain from human HYPA/FBP11.
M.Allen, A.Friedler, O.Schon, M.Bycroft.
The FF domain is a 60 amino acid residue phosphopeptide-binding module found in a variety of eukaryotic proteins including the transcription elongation factor CA150, the splicing factor Prp40 and p190RHOGAP. We have determined the structure of an FF domain from HYPA/FBP11. The domain is composed of three alpha helices arranged in an orthogonal bundle with a 3(10) helix in the loop between the second and third alpha helices. The structure differs from those of other phosphopeptide-binding domains and represents a novel phosphopeptide-binding fold.
  Selected figure(s)  
Figure 1.
Figure 1. (a) An overlay of the backbone atoms of the 25 lowest-energy NMR structures. The coding sequence for residues 357-425 of SPTREMBL O75400 corresponding to the FF domain was amplified by PCR from IMAGE cDNA clone 731611 (obtained from the MRC HGMP Resource Centre) by standard methods and cloned into a pRSET-derived pHisGro vector. This was used to over-express a soluble histidine-tagged GroEL apical domain/FF domain fusion protein in Escherichia coli. The fusion protein was purified under native conditions using NTA agarose (Qiagen). After cleavage with thrombin, the FF domain was purified using ion-exchange chromatography and gel-filtration. The samples for NMR spectroscopy typically contained 2.5 mM human FF domain in 90% H[2]O/10% 2H[2]O containing 50 mM KCl, 50 mM potassium phosphate (pH 6.0) at 298 K. The NMR spectra were assigned using standard NMR methods.[18. and 19.] The assignments have been deposited in the BioMagResBank under accession numbers PDB 1H40 BMRDB 5537. A set of distance constraints were derived from a series of NOESY spectra recorded in H[2]O and 2H[2]O with mixing times of 150 ms. The NOESY spectrum was integrated according to the cross-peak strengths and calibrated by comparison with NOE connectivities obtained for standard inter-residue distances within an a helix. After calibration, the NOE constraints were classified into the following categories: strong, medium, weak and very weak, corresponding to inter-proton distance constraints of 1.8-2.8 Å, 1.8-3.5 Å, 1.8-4.75 Å, and 2.5-6.0 Å, respectively. Hydrogen bond constraints were included for a number of backbone NH groups whose signals were observed in a 2D 1H-15N-HSQC recorded in 99.996% 2H[2]O at 298 K (pH 5.0). For hydrogen bond partners, two distance constraints were used where the distance (D)H-O(A) corresponded to 1.5-2.5 Å and (D)N-O(A) to 2.5-3.5 Å. Torsional angle constraints were obtained from an analysis of C', N, C^a Ha and C^b chemical shifts using the program TALOS.[20.] The three-dimensional structure of the FF domain was calculated using a dynamic simulated annealing protocol based upon the work of Nilges et al.[21.] in the program XPLOR (Brünger, A. T. (1992). X-PLOR Version 3.1: a system for cystallography and NMR, Yale University, New Haven, CT). The coordinates have been deposited in the protein structure database, entry. (b) A ribbon representation of the lowest-energy structure prepared using the program MOLSCRIPT.[22.] (c) A ribbon representation of the C-terminal region of human phosphatase 2C alpha prepared using the program MOLSCRIPT. [22.] Note there is a break in the electron density in the loop between the first and second helices.
Figure 2.
Figure 2. (a) Ribbon representation of the FF domain with the side-chains of the structural ensemble for the conserved residues in the hydrophobic core of the domain. (b) Structure-based sequence alignment of selected FF domains. Proteins included are the WW/FF domain-containing proteins that have been shown to bind to RNAP II CTD via their FF domains (mouse HYPA/FBP11(Q9R1C7), Saccharomyces cerevisiae PRP40 (PR40_YEAST), human CA150 (O14776)), human RHOGAP 190-A (Q9NRY4) and human RHOGAP 190-B (Q13017). Residues that are conserved in 50% of FF domains are indicated.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 323, 411-416) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21062759 A.Friedler (2011).
From peptides to proteins: lessons from my years at the Centre for Protein Engineering.
  Protein Eng Des Sel, 24, 241-245.  
20829478 D.M.Korzhnev, T.L.Religa, W.Banachewicz, A.R.Fersht, and L.E.Kay (2010).
A transient and low-populated protein-folding intermediate at atomic resolution.
  Science, 329, 1312-1316.
PDB code: 2kzg
19722265 R.Bonet, L.Ruiz, B.Morales, and M.J.Macias (2009).
Solution structure of the fourth FF domain of yeast Prp40 splicing factor.
  Proteins, 77, 1000-1003.
PDB code: 2kfd
18218711 B.Wu, A.Yee, Y.J.Huang, T.A.Ramelot, J.R.Cort, A.Semesi, J.W.Jung, W.Lee, G.T.Montelione, M.A.Kennedy, and C.H.Arrowsmith (2008).
The solution structure of ribosomal protein S17E from Methanobacterium thermoautotrophicum: a structural homolog of the FF domain.
  Protein Sci, 17, 583-588.
PDB code: 1rq6
19014439 C.Ester, and P.Uetz (2008).
The FF domains of yeast U1 snRNP protein Prp40 mediate interactions with Luc7 and Snu71.
  BMC Biochem, 9, 29.  
18536009 R.Bonet, X.Ramirez-Espain, and M.J.Macias (2008).
Solution structure of the yeast URN1 splicing factor FF domain: comparative analysis of charge distributions in FF domain structures-FFs and SURPs, two domains with a similar fold.
  Proteins, 73, 1001-1009.
PDB code: 2juc
18047689 C.S.Hackett, A.M.Geurts, and P.B.Hackett (2007).
Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy.
  Genome Biol, 8, S12.  
17464570 P.Lundström, P.Vallurupalli, T.L.Religa, F.W.Dahlquist, and L.E.Kay (2007).
A single-quantum methyl 13C-relaxation dispersion experiment with improved sensitivity.
  J Biomol NMR, 38, 79-88.  
17517666 T.L.Religa, C.M.Johnson, D.M.Vu, S.H.Brewer, R.B.Dyer, and A.R.Fersht (2007).
The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain.
  Proc Natl Acad Sci U S A, 104, 9272-9277.
PDB code: 2p81
16253993 A.Gasch, S.Wiesner, P.Martin-Malpartida, X.Ramirez-Espain, L.Ruiz, and M.J.Macias (2006).
The structure of Prp40 FF1 domain and its interaction with the crn-TPR1 motif of Clf1 gives a new insight into the binding mode of FF domains.
  J Biol Chem, 281, 356-364.
PDB code: 2b7e
16717285 A.M.Geurts, C.S.Hackett, J.B.Bell, T.L.Bergemann, L.S.Collier, C.M.Carlson, D.A.Largaespada, and P.B.Hackett (2006).
Structure-based prediction of insertion-site preferences of transposons into chromosomes.
  Nucleic Acids Res, 34, 2803-2811.  
16698547 C.Pastore, S.Adinolfi, M.A.Huynen, V.Rybin, S.Martin, M.Mayer, B.Bukau, and A.Pastore (2006).
YfhJ, a molecular adaptor in iron-sulfur cluster formation or a frataxin-like protein?
  Structure, 14, 857-867.
PDB code: 2bzt
16286474 E.Vojnic, B.Simon, B.D.Strahl, M.Sattler, and P.Cramer (2006).
Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that couples histone H3 Lys36 methylation to transcription.
  J Biol Chem, 281, 13-15.
PDB code: 2c5z
16565070 K.L.Damm, and H.A.Carlson (2006).
Gaussian-weighted RMSD superposition of proteins: a structural comparison for flexible proteins and predicted protein structures.
  Biophys J, 90, 4558-4573.  
15665873 C.G.Noble, D.Hollingworth, S.R.Martin, V.Ennis-Adeniran, S.J.Smerdon, G.Kelly, I.A.Taylor, and A.Ramos (2005).
Key features of the interaction between Pcf11 CID and RNA polymerase II CTD.
  Nat Struct Mol Biol, 12, 144-151.
PDB code: 2bf0
15466421 E.B.Gómez, V.T.Angeles, and S.L.Forsburg (2005).
A screen for Schizosaccharomyces pombe mutants defective in rereplication identifies new alleles of rad4+, cut9+ and psf2+.
  Genetics, 169, 77-89.  
16392943 J.M.Carr, and D.J.Wales (2005).
Global optimization and folding pathways of selected alpha-helical proteins.
  J Chem Phys, 123, 234901.  
15808743 L.Aravind, V.Anantharaman, S.Balaji, M.M.Babu, and L.M.Iyer (2005).
The many faces of the helix-turn-helix domain: transcription regulation and beyond.
  FEMS Microbiol Rev, 29, 231-262.  
16314571 M.Li, H.P.Phatnani, Z.Guan, H.Sage, A.L.Greenleaf, and P.Zhou (2005).
Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1.
  Proc Natl Acad Sci U S A, 102, 17636-17641.
PDB code: 2a7o
15629714 W.Jiang, R.Sordella, G.C.Chen, S.Hakre, A.L.Roy, and J.Settleman (2005).
An FF domain-dependent protein interaction mediates a signaling pathway for growth factor-induced gene expression.
  Mol Cell, 17, 23-35.  
14988499 G.A.Papoian, J.Ulander, M.P.Eastwood, Z.Luthey-Schulten, and P.G.Wolynes (2004).
Water in protein structure prediction.
  Proc Natl Acad Sci U S A, 101, 3352-3357.  
15456888 K.T.Lin, R.M.Lu, and W.Y.Tarn (2004).
The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo.
  Mol Cell Biol, 24, 9176-9185.  
15485897 M.J.Smith, S.Kulkarni, and T.Pawson (2004).
FF domains of CA150 bind transcription and splicing factors through multiple weak interactions.
  Mol Cell Biol, 24, 9274-9285.  
15096617 P.Jemth, S.Gianni, R.Day, B.Li, C.M.Johnson, V.Daggett, and A.R.Fersht (2004).
Demonstration of a low-energy on-pathway intermediate in a fast-folding protein by kinetics, protein engineering, and simulation.
  Proc Natl Acad Sci U S A, 101, 6450-6455.  
15480727 X.Sun, J.Zhao, K.Kylberg, T.Soop, K.Palka, E.Sonnhammer, N.Visa, A.T.Alzhanova-Ericsson, and B.Daneholt (2004).
Conspicuous accumulation of transcription elongation repressor hrp130/CA150 on the intron-rich Balbiani ring 3 gene.
  Chromosoma, 113, 244-257.  
12705864 R.Sordella, W.Jiang, G.C.Chen, M.Curto, and J.Settleman (2003).
Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis.
  Cell, 113, 147-158.  
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.