title: High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation.
abstract: The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 Å) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBP's concave DNA-binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation.
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Madhanagopal
authors.initials: M
authors.lastname: Anandapadamanaban
authors.forename: Cecilia
authors.initials: C
authors.lastname: Andresen
authors.forename: Sara
authors.initials: S
authors.lastname: Helander
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ohyama
authors.forename: Marina I
authors.initials: MI
authors.lastname: Siponen
authors.forename: Patrik
authors.initials: P
authors.lastname: Lundström
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kokubo
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
authors.forename: Martin
authors.initials: M
authors.lastname: Moche
authors.forename: Maria
authors.initials: M
authors.lastname: Sunnerhagen
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D005786:Gene Expression Regulation / Q000502:physiology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry* / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000737:chemistry* / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000378:metabolism; D035361:Transcription Factor TFIIIB / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C090956:BRF1 protein, S cerevisiae; C115017:SPT15 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C106785:TAF1 protein, S cerevisiae; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035362:Transcription Factor TFIID; D035361:Transcription Factor TFIIIB; D000251:Adenosine Triphosphatases; C073676:MOT1 protein, S cerevisiae