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PDBsum entry 1au7
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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
1au7

 

 

 

 

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Contents
Protein chains
130 a.a. *
DNA/RNA
Waters ×528
* Residue conservation analysis
PDB id:
1au7
Name: Transcription/DNA
Title: Pit-1 mutant/DNA complex
Structure: Consensus DNA 25-mer. Chain: c. Engineered: yes. DNA (5'- d( Cp Tp Tp Cp Cp Tp Cp Ap Tp Gp Tp Ap Tp Ap Tp Ap C p Ap Tp Gp Ap Gp Gp A)-3'). Chain: d. Engineered: yes. Protein pit-1.
Source: Synthetic: yes. Rattus norvegicus. Norway rat. Organism_taxid: 10116. Strain: sprague-dawley. Organ: pituitary gland. Tissue: endocrine. Cell: lactotropes, somatotropes. Cellular_location: nuclear.
Resolution:
2.30Å     R-factor:   0.230     R-free:   0.302
Authors: E.M.Jacobson,P.Li,A.Leon-Del-Rio,M.G.Rosenfeld,A.K.Aggarwal
Key ref: E.M.Jacobson et al. (1997). Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev, 11, 198-212. PubMed id: 9009203
Date:
12-Sep-97     Release date:   28-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10037  (PIT1_RAT) -  Pituitary-specific positive transcription factor 1 from Rattus norvegicus
Seq:
Struc: 		291 a.a.
130 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DNA/RNA chains
  T-C-C-T-C-A-T-G-T-A-T-A-T-A-C-A-T-G-A-G-G-A-A-G-G 25 bases
  C-T-T-C-C-T-C-A-T-G-T-A-T-A-T-A-C-A-T-G-A-G-G-A 24 bases

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Genes Dev 11:198-212 (1997)
PubMed id: 9009203  
 
 
Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.
E.M.Jacobson, P.Li, A.Leon-del-Rio, M.G.Rosenfeld, A.K.Aggarwal.
 
  ABSTRACT  
 
Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21117060 R.Jauch, S.H.Choo, C.K.Ng, and P.R.Kolatkar (2011).
Crystal structure of the dimeric Oct6 (POU3f1) POU domain bound to palindromic MORE DNA.
  Proteins, 79, 674-677.
PDB code: 2xsd
21187427 W.Banachewicz, C.M.Johnson, and A.R.Fersht (2011).
Folding of the Pit1 homeodomain near the speed limit.
  Proc Natl Acad Sci U S A, 108, 569-573.  
21422286 W.Banachewicz, T.L.Religa, R.D.Schaeffer, V.Daggett, and A.R.Fersht (2011).
Malleability of folding intermediates in the homeodomain superfamily.
  Proc Natl Acad Sci U S A, 108, 5596-5601.  
20005866 C.B.McDonald, K.L.Seldeen, B.J.Deegan, V.Bhat, and A.Farooq (2010).
Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control.
  Arch Biochem Biophys, 494, 216-225.  
20371823 L.Bai, and J.R.Carlson (2010).
Distinct functions of acj6 splice forms in odor receptor gene choice.
  J Neurosci, 30, 5028-5036.  
20064932 Y.Cao, F.Oswald, S.A.Wacker, K.Bundschu, and W.Knöchel (2010).
Reversal of Xenopus Oct25 function by disruption of the POU domain structure.
  J Biol Chem, 285, 8408-8421.  
18511808 A.J.Okumura, L.F.Peterson, F.Okumura, A.Boyapati, and D.E.Zhang (2008).
t(8;21)(q22;q22) Fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression.
  Blood, 112, 1392-1401.  
18187506 P.K.Purbey, S.Singh, P.P.Kumar, S.Mehta, K.N.Ganesh, D.Mitra, and S.Galande (2008).
PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1.
  Nucleic Acids Res, 36, 2107-2122.  
18440973 P.Peixoto, Y.Liu, S.Depauw, M.P.Hildebrand, D.W.Boykin, C.Bailly, W.D.Wilson, and M.H.David-Cordonnier (2008).
Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication.
  Nucleic Acids Res, 36, 3341-3353.  
18075577 J.Kuriyan, and D.Eisenberg (2007).
The origin of protein interactions and allostery in colocalization.
  Nature, 450, 983-990.  
17652321 K.Yamasaki, T.Akiba, T.Yamasaki, and K.Harata (2007).
Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1.
  Nucleic Acids Res, 35, 5073-5084.
PDB codes: 2o49 2o4a
17576670 R.Alazard, L.Mourey, C.Ebel, P.V.Konarev, M.V.Petoukhov, D.I.Svergun, and M.Erard (2007).
Fine-tuning of intrinsic N-Oct-3 POU domain allostery by regulatory DNA targets.
  Nucleic Acids Res, 35, 4420-4432.  
16914737 B.M.Shewchuk, Y.Ho, S.A.Liebhaber, and N.E.Cooke (2006).
A single base difference between Pit-1 binding sites at the hGH promoter and locus control region specifies distinct Pit-1 conformations and functions.
  Mol Cell Biol, 26, 6535-6546.  
16908544 I.A.Demarco, T.C.Voss, C.F.Booker, and R.N.Day (2006).
Dynamic interactions between Pit-1 and C/EBPalpha in the pituitary cell nucleus.
  Mol Cell Biol, 26, 8087-8098.  
16879162 M.H.Quentien, A.Barlier, J.L.Franc, I.Pellegrini, T.Brue, and A.Enjalbert (2006).
Pituitary transcription factors: from congenital deficiencies to gene therapy.
  J Neuroendocrinol, 18, 633-642.  
16357834 M.Heidari, K.L.Rice, J.K.Phillips, U.R.Kees, and W.K.Greene (2006).
The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells.
  Leukemia, 20, 304-312.  
  15844473 G.Gat-Yablonski, A.Klar, D.Hirsch, A.Eliakim, L.Lazar, H.Hurvitz, and M.Phillip (2005).
Three novel mutations in POU1F1 in Israeli patients with combined pituitary hormone deficiency.
  J Pediatr Endocrinol Metab, 18, 385-393.  
15767276 R.Alazard, M.Blaud, S.Elbaz, C.Vossen, G.Icre, G.Joseph, L.Nieto, and M.Erard (2005).
Identification of the 'NORE' (N-Oct-3 responsive element), a novel structural motif and composite element.
  Nucleic Acids Res, 33, 1513-1523.  
15726414 Y.I.Chi (2005).
Homeodomain revisited: a lesson from disease-causing mutations.
  Hum Genet, 116, 433-444.  
12554749 J.F.Enwright, M.A.Kawecki-Crook, T.C.Voss, F.Schaufele, and R.N.Day (2003).
A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription.
  Mol Endocrinol, 17, 209-222.  
14580198 K.J.Hwang, B.Xiang, J.M.Gruschus, K.Y.Nam, K.T.No, M.Nirenberg, and J.A.Ferretti (2003).
Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound to DNA induced by an embryonically lethal A35T point mutation.
  Biochemistry, 42, 12522-12531.
PDB code: 1qry
12727885 K.Lins, A.Reményi, A.Tomilin, S.Massa, M.Wilmanns, P.Matthias, and H.R.Schöler (2003).
OBF1 enhances transcriptional potential of Oct1.
  EMBO J, 22, 2188-2198.  
12780757 K.McLennan, Y.Jeske, A.Cotterill, D.Cowley, J.Penfold, T.Jones, N.Howard, M.Thomsett, and C.Choong (2003).
Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates.
  Clin Endocrinol (Oxf), 58, 785-794.  
12554785 R.N.Day, T.C.Voss, J.F.Enwright, C.F.Booker, A.Periasamy, and F.Schaufele (2003).
Imaging the localized protein interactions between Pit-1 and the CCAAT/enhancer binding protein alpha in the living pituitary cell nucleus.
  Mol Endocrinol, 17, 333-345.  
12904605 S.Malvagia, G.M.Poggi, E.Pasquini, M.A.Donati, I.Pela, A.Morrone, and E.Zammarchi (2003).
The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient.
  Pediatr Res, 54, 635-640.  
12242337 K.D.Augustijn, D.L.Duval, R.Wechselberger, R.Kaptein, A.Gutierrez-Hartmann, and P.C.van der Vliet (2002).
Structural characterization of the PIT-1/ETS-1 interaction: PIT-1 phosphorylation regulates PIT-1/ETS-1 binding.
  Proc Natl Acad Sci U S A, 99, 12657-12662.  
12414730 S.Hovde, C.S.Hinkley, K.Strong, A.Brooks, L.Gu, R.W.Henry, and J.Geiger (2002).
Activator recruitment by the general transcription machinery: X-ray structural analysis of the Oct-1 POU domain/human U1 octamer/SNAP190 peptide ternary complex.
  Genes Dev, 16, 2772-2777.  
12453420 Y.I.Chi, J.D.Frantz, B.C.Oh, L.Hansen, S.Dhe-Paganon, and S.E.Shoelson (2002).
Diabetes mutations delineate an atypical POU domain in HNF-1alpha.
  Mol Cell, 10, 1129-1137.
PDB code: 1ic8
11861910 Z.Morávek, S.Neidle, and B.Schneider (2002).
Protein and drug interactions in the minor groove of DNA.
  Nucleic Acids Res, 30, 1182-1191.  
11583619 A.Reményi, A.Tomilin, E.Pohl, K.Lins, A.Philippsen, R.Reinbold, H.R.Schöler, and M.Wilmanns (2001).
Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping.
  Mol Cell, 8, 569-580.
PDB codes: 1e3o 1hf0
11136971 A.Tomilin, A.Reményi, K.Lins, H.Bak, S.Leidel, G.Vriend, M.Wilmanns, and H.R.Schöler (2000).
Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration.
  Cell, 103, 853-864.  
11029584 D.J.Smit, A.G.Smith, P.G.Parsons, G.E.Muscat, and R.A.Sturm (2000).
Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors.
  Eur J Biochem, 267, 6413-6422.  
10848606 I.Röckelein, S.Röhrig, R.Donhauser, S.Eimer, and R.Baumeister (2000).
Identification of amino acid residues in the Caenorhabditis elegans POU protein UNC-86 that mediate UNC-86-MEC-3-DNA ternary complex formation.
  Mol Cell Biol, 20, 4806-4813.  
10613862 P.Manna, R.P.Nieder, and M.R.Schaefer (2000).
DNA-Binding properties of the Fremyella diplosiphon RpbA repressor.
  J Bacteriol, 182, 51-56.  
11149379 S.Harvey, Y.Azumaya, and K.L.Hull (2000).
Pituitary and extrapituitary growth hormone: Pit-1 dependence?
  Can J Physiol Pharmacol, 78, 1013-1028.  
10899123 S.Röhrig, I.Röckelein, R.Donhauser, and R.Baumeister (2000).
Protein interaction surface of the POU transcription factor UNC-86 selectively used in touch neurons.
  EMBO J, 19, 3694-3703.  
10588713 C.Kioussi, S.O'Connell, L.St-Onge, M.Treier, A.S.Gleiberman, P.Gruss, and M.G.Rosenfeld (1999).
Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development.
  Proc Natl Acad Sci U S A, 96, 14378-14382.  
10541551 D.Chasman, K.Cepek, P.A.Sharp, and C.O.Pabo (1999).
Crystal structure of an OCA-B peptide bound to an Oct-1 POU domain/octamer DNA complex: specific recognition of a protein-DNA interface.
  Genes Dev, 13, 2650-2657.
PDB code: 1cqt
10572243 G.Kausel, M.I.Vera, R.San Martin, J.Figueroa, A.Molina, M.Muller, J.Martial, and M.Krauskopf (1999).
Transcription factor pit-1 expression is modulated upon seasonal acclimatization of eurythermal ectotherms: identification of two pit-1 genes in the carp.
  J Cell Biochem, 75, 598-609.  
  10346815 H.E.Xu, M.A.Rould, W.Xu, J.A.Epstein, R.L.Maas, and C.O.Pabo (1999).
Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding.
  Genes Dev, 13, 1263-1275.
PDB code: 6pax
10508698 J.S.Dasen, and M.G.Rosenfeld (1999).
Combinatorial codes in signaling and synergy: lessons from pituitary development.
  Curr Opin Genet Dev, 9, 566-574.  
10367888 J.S.Dasen, S.M.O'Connell, S.E.Flynn, M.Treier, A.S.Gleiberman, D.P.Szeto, F.Hooshmand, A.K.Aggarwal, and M.G.Rosenfeld (1999).
Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types.
  Cell, 97, 587-598.  
10481164 L.E.Cohen, S.Radovick, and F.E.Wondisford (1999).
Transcription Factors and Hypopituitarism.
  Trends Endocrinol Metab, 10, 326-332.  
10022514 M.G.Mancini, B.Liu, Z.D.Sharp, and M.A.Mancini (1999).
Subnuclear partitioning and functional regulation of the Pit-1 transcription factor.
  J Cell Biochem, 72, 322-338.  
  10082571 T.Kophengnavong, A.S.Carroll, and T.K.Blackwell (1999).
The SKN-1 amino-terminal arm is a DNA specificity segment.
  Mol Cell Biol, 19, 3039-3050.  
9519292 A.K.Aggarwal, and D.A.Wah (1998).
Novel site-specific DNA endonucleases.
  Curr Opin Struct Biol, 8, 19-25.  
  9819426 P.Sauter, and P.Matthias (1998).
Coactivator OBF-1 makes selective contacts with both the POU-specific domain and the POU homeodomain and acts as a molecular clamp on DNA.
  Mol Cell Biol, 18, 7397-7409.  
9724717 S.Rhee, R.G.Martin, J.L.Rosner, and D.R.Davies (1998).
A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator.
  Proc Natl Acad Sci U S A, 95, 10413-10418.
PDB code: 1bl0
9519295 S.Tan, and T.J.Richmond (1998).
Eukaryotic transcription factors.
  Curr Opin Struct Biol, 8, 41-48.  
  9649510 V.Botquin, H.Hess, G.Fuhrmann, C.Anastassiadis, M.K.Gross, G.Vriend, and H.R.Schöler (1998).
New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2.
  Genes Dev, 12, 2073-2090.  
9237997 M.A.Cleary, P.S.Pendergrast, and W.Herr (1997).
Structural flexibility in transcription complex formation revealed by protein-DNA photocrosslinking.
  Proc Natl Acad Sci U S A, 94, 8450-8455.  
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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