title: Structural and functional characterization of an atypical activation domain in erythroid Kruppel-like factor (EKLF).
abstract: Erythroid Krüppel-like factor (EKLF) plays an important role in erythroid development by stimulating β-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 α-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.
authors.affiliation: Département de Biochimie, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, Canada QC H3C 3J7.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mas
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lussier-Price
authors.forename: Shefali
authors.initials: S
authors.lastname: Soni
authors.forename: Thomas
authors.initials: T
authors.lastname: Morse
authors.forename: Geneviève
authors.initials: G
authors.lastname: Arseneault
authors.forename: Paola
authors.initials: P
authors.lastname: Di Lello
authors.forename: Julien
authors.initials: J
authors.lastname: Lafrance-Vanasse
authors.forename: James J
authors.initials: JJ
authors.lastname: Bieker
authors.forename: James G
authors.initials: JG
authors.lastname: Omichinski
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002151:Calorimetry; D003001:Cloning, Molecular; D006801:Humans; D020014:K562 Cells; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor