Structural and functional characterization of an atypical activation domain in erythroid Krüppel-like factor (EKLF)

Caroline Mas, Mathieu Lussier-Price, Shefali Soni, Thomas Morse, Geneviève Arseneault, Paola Di Lello, Julien Lafrance-Vanasse, James J. Bieker, James G. Omichinski

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Erythroid Krüppel-like factor (EKLF) plays an important role in erythroid development by stimulating ß-globin gene expression. We have examined the details by which the minimal transactivation domain (TAD) of EKLF (EKLFTAD) interacts with several transcriptional regulatory factors. We report that EKLFTAD displays homology to the p53TAD and, like the p53TAD, can be divided into two functional subdomains (EKLFTAD1 and EKLFTAD2). Based on sequence analysis, we found that EKLFTAD2 is conserved in KLF2, KLF4, KLF5, and KLF15. In addition, we demonstrate that EKLFTAD2 binds the amino-terminal PH domain of the Tfb1/p62 subunit of TFIIH (Tfb1PH/p62PH) and four domains of CREB-binding protein/p300. The solution structure of the EKLFTAD2/Tfb1PH complex indicates that EKLFTAD2 binds Tfb1PH in an extended conformation, which is in contrast to the a-helical conformation seen for p53TAD2 in complex with Tfb1PH. These studies provide detailed mechanistic information into EKLFTAD functions as well as insights into potential interactions of the TADs of other KLF proteins. In addition, they suggest that not only have acidic TADs evolved so that they bind using different conformations on a common target, but that transitioning from a disordered to a more ordered state is not a requirement for their ability to bind multiple partners.

Original languageEnglish
Pages (from-to)10484-10489
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number26
DOIs
StatePublished - 28 Jun 2011

Keywords

  • Hematopoiesis
  • Intrinsically unstructured domain
  • NMR spectroscopy
  • Transcription factor IIE
  • Transcriptional activators

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