Sequence-dependent solution structure and motions of 13 TATA/TBP (TATA-box binding protein) complexes

Daniel Strahs, Danny Barash, Xiaoliang Qian, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

The TATA element is a well-known example of a DNA promoter sequence recognized by the TATA box binding protein (TBP) through its intrinsic motion and deformability. Although TBP recognizes the TATA element octamer unusually (through the minor groove, which lacks the distinctive features of the major groove), single base-pair replacements alter transcriptional activity. Recent crystallographic experiments have suggested that TATA/TBP complexes differing by a single base pair retain substantial structural similarity despite their functional differences in activating transcription. To investigate the subtle role of sequence-dependent motion within the TATA element and certain aspects of its effect on assembly of the transcriptional complex, we examine 5-ns dynamics trajectories of 13 variant TATA/TBP complexes differing from each other by a single base pair. They include the wild-type (WT) adenovirus 2 major late promoter (AdMLP) TATA element, TATAAAAG (the octamer specifies positions -31 to -24 with respect to the transcription initiation site), and the variants A31 (i.e., AATAAAAG), T30, A29, C29, G28, T28, T27, G26, T26, C25, T25, and T24. Our simulated TATA/TBP complexes develop sequence- dependent structure and motion trends that may lead to favorable orientations for high-activity variants (with respect to binding TFIIA, TFIIB, and other transcription factors), while conversely, accelerate dissociation of low-activity TATA/TBP complexes. The motions that promote favorable geometries for preinitiation complexes include small rotations between TBP's N- and C-terminal domains, sense strand DNA backbone "slithering, " and rotations in TBP's H2 and H2′ helices. Low-activity variants tend to translate the H1 and H1′ helices and withdraw the intercalating phenylalanines. These cumulative DNA and protein motions lead to a spatial spread of complex orientations up to 4 Å; this is associated with an overall bend of the variant TATA/TBP complexes that spans 93° to 110° (107° for the crystal reference). Taken together, our analyses imply larger differences when these local structural and bending changes are extended to longer DNA (upstream and downstream) and suggest that specific local TATA/TBP motions (e.g., shifts in TBP helices and TATA bases and backbone) play a role in modulating the formation and maintenance of the transcription initiation complex.

Original languageEnglish (US)
Pages (from-to)216-243
Number of pages28
JournalBiopolymers - Peptide Science Section
Volume69
Issue number2
DOIs
StatePublished - Jun 2003

Fingerprint

TATA-Box Binding Protein
Transcription
Base Pairing
Transcription Factor TFIIA
Transcription Factor TFIIB
N,N-dimethyl-3,3-diphenyl-1-methylallylamine
Carrier Proteins
Transcription factors
Transcription Initiation Site
Formability
Phenylalanine
Adenoviridae
Transcription Factors
Trajectories
Maintenance
Proteins

Keywords

  • Global motions
  • Sequence-dependent bending
  • Solvent interactions
  • TATA box binding protein
  • TATA variants
  • Transcriptional activity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Sequence-dependent solution structure and motions of 13 TATA/TBP (TATA-box binding protein) complexes. / Strahs, Daniel; Barash, Danny; Qian, Xiaoliang; Schlick, Tamar.

In: Biopolymers - Peptide Science Section, Vol. 69, No. 2, 06.2003, p. 216-243.

Research output: Contribution to journalArticle

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