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

Xiaoping Wang, Dagmar M. Truckses, Shinako Takada, Tatsushi Matsumura, Naoko Tanese, Raymond H. Jacobson

Research output: Contribution to journalArticle

31 Citations (Scopus)

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-Å 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, DΨΨζζPsi;Φ, 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.

Original languageEnglish
Pages (from-to)7839-7844
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number19
DOIs
Publication statusPublished - May 8 2007
Externally publishedYes

Keywords

  • TAFH domain
  • TFIID
  • Transcription
  • X-ray crystallography

ASJC Scopus subject areas

  • General

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