Busby S, Ebright R H
School of Biosciences, The University of Birmingham, Birmingham, B15 2TT, UK.
J Mol Biol. 1999 Oct 22;293(2):199-213. doi: 10.1006/jmbi.1999.3161.
Transcription activation by Escherichia coli catabolite activator protein (CAP) at each of two classes of simple CAP-dependent promoters is understood in structural and mechanistic detail. At class I CAP-dependent promoters, CAP activates transcription from a DNA site located upstream of the DNA site for RNA polymerase holoenzyme (RNAP); at these promoters, transcription activation involves protein-protein interactions between CAP and the RNAP alpha subunit C-terminal domain that facilitate binding of RNAP to promoter DNA to form the RNAP-promoter closed complex. At class II CAP-dependent promoters, CAP activates transcription from a DNA site that overlaps the DNA site for RNAP; at these promoters, transcription activation involves both: (i) protein-protein interactions between CAP and RNAP alpha subunit C-terminal domain that facilitate binding of RNAP to promoter DNA to form the RNAP-promoter closed complex; and (ii) protein-protein interactions between CAP and RNAP alpha subunit N-terminal domain that facilitates isomerization of the RNAP-promoter closed complex to the RNAP-promoter open complex. Straightforward combination of the mechanisms for transcription activation at class I and class II CAP-dependent promoters permits synergistic transcription activation by multiple molecules of CAP, or by CAP and other activators. Interference with determinants of CAP or RNAP involved in transcription activation at class I and class II CAP-dependent promoters permits "anti-activation" by negative regulators. Basic features of transcription activation at class I and class II CAP-dependent promoters appear to be generalizable to other activators.
大肠杆菌分解代谢物激活蛋白(CAP)在两类简单的CAP依赖性启动子上的转录激活作用,在结构和机制细节方面已得到充分理解。在I类CAP依赖性启动子中,CAP从位于RNA聚合酶全酶(RNAP)DNA结合位点上游的DNA位点激活转录;在这些启动子处,转录激活涉及CAP与RNAPα亚基C末端结构域之间的蛋白质-蛋白质相互作用,这种相互作用促进RNAP与启动子DNA结合形成RNAP-启动子闭合复合物。在II类CAP依赖性启动子中,CAP从与RNAP的DNA结合位点重叠的DNA位点激活转录;在这些启动子处,转录激活涉及两方面:(i)CAP与RNAPα亚基C末端结构域之间的蛋白质-蛋白质相互作用,促进RNAP与启动子DNA结合形成RNAP-启动子闭合复合物;(ii)CAP与RNAPα亚基N末端结构域之间的蛋白质-蛋白质相互作用,促进RNAP-启动子闭合复合物异构化为RNAP-启动子开放复合物。I类和II类CAP依赖性启动子转录激活机制的直接组合,允许多个CAP分子或CAP与其他激活剂协同激活转录。干扰I类和II类CAP依赖性启动子转录激活中涉及的CAP或RNAP的决定因素,可使负调节因子产生“反激活”作用。I类和II类CAP依赖性启动子转录激活的基本特征似乎可推广到其他激活剂。