Structural diversity in p160/CREB-binding protein coactivator complexes

Ligand-induced transcription by nuclear receptors involves the recruitment of p160 coactivators such as steroid receptor coactivator 1 (SRC1), in complex with histone acetyltransferases such as CREB-binding protein (CBP) and p300. Here we describe the solution structure of a complex formed by the SRC1 interaction domain (SID) of CBP and the activation domain (AD1) of SRC1, both of which contain four helical regions (C alpha 1, C alpha 2, C alpha 3, and C alpha 3' in CBP and S alpha 1, S alpha 2', S alpha 2, and S alpha 3 in SRC1). A tight four-helix bundle is formed between S alpha 1, C alpha 1, C alpha 2, and C alpha 3 that is capped by S alpha 3. In contrast to the structure of the AD1 domain of the related p160 protein ACTR in complex with CBP SID, the sequences forming S alpha 2' and S alpha 2 in SRC1 AD1 are not involved in the interface between the two domains but rather serve to position S alpha 3. Thus, although the CBP SID domain adopts a similar fold in complex with different p160 proteins, the topologies of the AD1 domains are strikingly different, a feature that is likely to contribute to functional specificity of these coactivator complexes.