Conserved region I of human coactivator TAF4 binds to a short hydrophobic motif present in transcriptional regulators.

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  • Author(s): Wang X;Wang X; Truckses DM; Takada S; Matsumura T; Tanese N; Jacobson RH
  • Source:
    Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 May 08; Vol. 104 (19), pp. 7839-44. Date of Electronic Publication: 2007 May 01.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      TATA-Binding Protein Associated Factors/*chemistry ; Transcription Factor TFIID/*chemistry; Amino Acid Motifs ; Amino Acid Sequence ; Basic-Leucine Zipper Transcription Factors/chemistry ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; Cyclic AMP Response Element-Binding Protein/chemistry ; Humans ; Molecular Sequence Data ; Protein Structure, Tertiary ; TATA-Binding Protein Associated Factors/physiology ; Transcription Factor TFIID/physiology
    • Abstract:
      TBP-associated factor 4 (TAF4), an essential subunit of the TFIID complex acts as a coactivator for multiple transcriptional regulators, including Sp1 and CREB. However, little is known regarding the structural properties of the TAF4 subunit that lead to the coactivator function. Here, we report the crystal structure at 2.0-A resolution of the human TAF4-TAFH domain, a conserved domain among all metazoan TAF4, TAF4b, and ETO family members. The hTAF4-TAFH structure adopts a completely helical fold with a large hydrophobic groove that forms a binding surface for TAF4 interacting factors. Using peptide phage display, we have characterized the binding preference of the hTAF4-TAFH domain for a hydrophobic motif, DPsiPsizetazetaPsiPhi, that is present in a number of nuclear factors, including several important transcriptional regulators with roles in activating, repressing, and modulating posttranslational modifications. A comparison of the hTAF4-TAFH structure with the homologous ETO-TAFH domain reveals several critical residues important for hTAF4-TAFH target specificity and suggests that TAF4 has evolved in response to the increased transcriptional complexity of metazoans.
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    • Grant Information:
      R01 GM069769 United States GM NIGMS NIH HHS; GM069769 United States GM NIGMS NIH HHS
    • Molecular Sequence:
      PDB 2P6V
    • Accession Number:
      0 (Basic-Leucine Zipper Transcription Factors)
      0 (CREB3 protein, human)
      0 (CREBZF protein, human)
      0 (Cyclic AMP Response Element-Binding Protein)
      0 (TAF4 protein, human)
      0 (TATA-Binding Protein Associated Factors)
      0 (Transcription Factor TFIID)
    • Publication Date:
      Date Created: 20070508 Date Completed: 20070607 Latest Revision: 20241125
    • Publication Date:
      20241126
    • Accession Number:
      PMC1876534
    • Accession Number:
      10.1073/pnas.0608570104
    • Accession Number:
      17483474