The transcriptional coactivators CBP and p300 are critical regulators of me
tazoan gene expression. They associate with many different DNA-bound transc
ription factors through small, conserved domains. We have identified a comp
actly folded 46 residue domain in CBP and p300, the IRF-3 binding domain (I
BiD), and we have determined its structure by NMR. It has a helical framewo
rk containing an apparently flexible polyglutamine loop that participates i
n ligand binding. Spectroscopic data indicate that induced folding accompan
ies association of IBiD with its partners, which exhibit no evident sequenc
e similarities. We demonstrate the significance both in vitro and in vivo o
f interactions between IBiD and a number of diverse partners. Thus, IBiD is
an important contributor to signal integration by CBP and p300.