Waters Lorna, Yue Baigong, Veverka Vaclav, Renshaw Philip, Bramham Janice, Matsuda Sachiko, Frenkiel Thomas, Kelly Geoffrey, Muskett Frederick, Carr Mark, Heery David M
Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
J Biol Chem. 2006 May 26;281(21):14787-95. doi: 10.1074/jbc.M600237200. Epub 2006 Mar 15.
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 (Calpha1, Calpha2, Calpha3, and Calpha3' in CBP and Salpha1, Salpha2', Salpha2, and Salpha3 in SRC1). A tight four-helix bundle is formed between Salpha1, Calpha1, Calpha2, and Calpha3 that is capped by Salpha3. In contrast to the structure of the AD1 domain of the related p160 protein ACTR in complex with CBP SID, the sequences forming Salpha2' and Salpha2 in SRC1 AD1 are not involved in the interface between the two domains but rather serve to position Salpha3. 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.
核受体的配体诱导转录涉及募集p160共激活因子，如类固醇受体共激活因子1（SRC1），其与组蛋白乙酰转移酶如CREB结合蛋白（CBP）和p300形成复合物。在此，我们描述了由CBP的SRC1相互作用结构域（SID）和SRC1的激活结构域（AD1）形成的复合物的溶液结构，这两个结构域均包含四个螺旋区域（CBP中的Calpha1、Calpha2、Calpha3和Calpha3'以及SRC1中的Salpha1、Salpha2'、Salpha2和Salpha3）。在Salpha1、Calpha1、Calpha2和Calpha3之间形成了一个紧密的四螺旋束，并由Salpha3封端。与相关p160蛋白ACTR的AD1结构域与CBP SID形成的复合物的结构相反，SRC1 AD1中形成Salpha2'和Salpha2的序列不参与两个结构域之间的界面，而是用于定位Salpha3。因此，尽管CBP SID结构域与不同的p160蛋白形成复合物时采用相似的折叠方式，但AD1结构域的拓扑结构却显著不同，这一特征可能有助于这些共激活因子复合物的功能特异性。
