title: Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain.
abstract: Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. Our results provide a model for understanding the regulation of genome-wide gene expression during development by TEA/ATTS family of transcription factors.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Asokan
authors.initials: A
authors.lastname: Anbanandam
authors.forename: Diana C
authors.initials: DC
authors.lastname: Albarado
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Nguyen
authors.forename: Georg
authors.initials: G
authors.lastname: Halder
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Gao
authors.forename: Sudha
authors.initials: S
authors.lastname: Veeraraghavan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA