Sequence-Dependent Solution Structure and Motions of 13
The TATA element DNA is a well-known example of a 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 basepair replacements alter transcriptional activity.
Recent crystallographic experiments have suggested that TATA/TBP complexes
differing by a single basepair 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 basepair.
They include the wildtype (WT) 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
pre-initiation 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\sugar\ helices
and withdraw the intercalating phenylalanines.
These cumulative DNA and protein motions
lead to a spatial spread of complex orientations up to 4 Angstroms;
this is associated with an overall bend of the variant TATA/TBP
complexes that spans 93 degrees
to 110 degrees (107 degrees 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.
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