Pittard James, Camakaris Helen, Yang Ji
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
Mol Microbiol. 2005 Jan;55(1):16-26. doi: 10.1111/j.1365-2958.2004.04385.x.
The TyrR protein of Escherichia coli can act both as a repressor and as an activator of transcription. It can interact with each of the three aromatic amino acids, with ATP and, under certain circumstances, with the C-terminal region of the alpha-subunit of RNA polymerase. TyrR protein is a dimer in solution but in the presence of tyrosine and ATP it self-associates to form a hexamer. Whereas TyrR dimers can, in the absence of any aromatic amino acids, bind to certain recognition sequences referred to as 'strong TyrR boxes', hexamers can bind to extended sequences including lower-affinity sites called 'weak TyrR boxes', some of which overlap the promoter. There is no single mechanism for repression, which in some cases involves exclusion of RNA polymerase from the promoter and in others, interference with the ability of bound RNA polymerase to form open complexes or to exit the promoter. When bound to a site upstream of certain promoters, TyrR protein in the presence of phenylalanine, tyrosine or tryptophan can interact with the alpha-subunit of RNA polymerase to activate transcription. In one unusual case, activation of a non-productive promoter is used to repress transcription from a promoter on the opposite strand. Regulation of individual transcription units within the regulon reflects their physiological function and is determined by the position and nature of the recognition sites (TyrR boxes) associated with each of the promoters. The intracellular levels of the various forms of the TyrR protein are also postulated to be of critical importance in determining regulatory outcomes. TyrR protein remains a paradigm for a regulator that is able to interact with multiple cofactors and exert a range of regulatory effects by forming different oligomers on DNA and making contact with other proteins. A recent analysis identifying putative TyrR boxes in the E. coli genome raises the possibility that the TyrR regulon may extend beyond the well-characterized transcription units described in this review.
大肠杆菌的TyrR蛋白既可以作为转录抑制因子，也可以作为转录激活因子。它能够与三种芳香族氨基酸中的每一种相互作用，还能与ATP相互作用，并且在某些情况下与RNA聚合酶α亚基的C末端区域相互作用。TyrR蛋白在溶液中是二聚体，但在酪氨酸和ATP存在的情况下会自我缔合形成六聚体。在没有任何芳香族氨基酸的情况下，TyrR二聚体可以结合到某些被称为“强TyrR框”的识别序列上，而六聚体则可以结合到更长的序列上，包括被称为“弱TyrR框”的低亲和力位点，其中一些与启动子重叠。不存在单一的抑制机制，在某些情况下，抑制涉及将RNA聚合酶排除在启动子之外，而在其他情况下，则是干扰结合的RNA聚合酶形成开放复合物或离开启动子的能力。当TyrR蛋白在苯丙氨酸、酪氨酸或色氨酸存在的情况下结合到某些启动子上游的位点时，它可以与RNA聚合酶的α亚基相互作用以激活转录。在一个不寻常的例子中，一个非生产性启动子的激活被用于抑制相反链上一个启动子的转录。操纵子内各个转录单元的调控反映了它们的生理功能，并由与每个启动子相关的识别位点（TyrR框）的位置和性质决定。各种形式的TyrR蛋白的细胞内水平也被认为对于确定调控结果至关重要。TyrR蛋白仍然是一个调控因子的范例——它能够与多种辅因子相互作用，并通过在DNA上形成不同的寡聚体以及与其他蛋白质接触来发挥一系列的调控作用。最近一项在大肠杆菌基因组中鉴定出假定的TyrR框的分析提出了一种可能性，即TyrR操纵子可能延伸到本综述中描述的那些特征明确的转录单元之外。
