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 (Cα1, Cα2, Cα3, and Cα3′ in CBP and Sα1, Sα2′, Sα2, and Sα3 in SRC1). A tight four-helix bundle is formed between Sα1, Cα1, Cα2, and Cα3 that is capped by Sα3. In contrast to the structure of the AD1 domain of the related p160 protein ACTR in complex with CBP SID, the sequences forming Sα2′ and Sα2 in SRC1 AD1 are not involved in the interface between the two domains but rather serve to position Sα3. 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.