Sequence-specific
DNA-binding activators, key regulators of gene expression, stimulate transcription in part by targeting the core promoter recognition
TFIID complex and aiding in its recruitment to promoter
DNA. Although it has been established that activators can interact with multiple components of
TFIID, it is unknown whether common or distinct surfaces within
TFIID are targeted by activators and what changes if any in the structure of
TFIID may occur upon binding activators. As a first step toward structurally dissecting activator/
TFIID interactions, we determined the three-dimensional structures of
TFIID bound to three distinct activators (i.e., the
tumor suppressor p53
protein,
glutamine-rich Sp1 and the
oncoprotein c-Jun) and compared their structures as determined by electron microscopy and single-particle reconstruction. By a combination of EM and biochemical mapping analysis, our results uncover distinct contact regions within
TFIID bound by each activator. Unlike the coactivator CRSP/
Mediator complex that undergoes drastic and global structural changes upon activator binding, instead, a rather confined set of local conserved structural changes were observed when each activator binds holo-
TFIID. These results suggest that activator contact may induce unique structural features of
TFIID, thus providing nanoscale information on activator-dependent
TFIID assembly and transcription initiation.