Assessing the permissiveness of transcriptional activator binding sites

Abstract

Both genetic and biochemical data suggest that transcriptional activators with little sequence homology nevertheless function through interaction with a shared group of coactivators. Here we show that a series of peptidomimetic transcriptional activation domains interact under cell-fiee and cellular conditions with the metazoan coactivator CBP despite differences in the positioning and identity of the constituent functional groups. Taken together, these results suggest that a key activator binding site within CBP is permissive, accepting multiple arrangements of hydrophobic functional groups. Further, this permissiveness is also observed with a coactivator from S. cerevisiae . Thus, the design of small molecule mimics of transcriptional activation domains with broad function may be more straightforward than previously envisioned. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 578–581, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com