Ramos Juan L, Martínez-Bueno Manuel, Molina-Henares Antonio J, Terán Wilson, Watanabe Kazuya, Zhang Xiaodong, Gallegos María Trinidad, Brennan Richard, Tobes Raquel
Department of Plant Biochemistry and Molecular and Cellular Biology, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Cientificas, Granada, Spain.
Microbiol Mol Biol Rev. 2005 Jun;69(2):326-56. doi: 10.1128/MMBR.69.2.326-356.2005.
We have developed a general profile for the proteins of the TetR family of repressors. The stretch that best defines the profile of this family is made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three-dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known. We have detected a set of 2,353 nonredundant proteins belonging to this family by screening genome and protein databases with the TetR profile. Proteins of the TetR family have been found in 115 genera of gram-positive, alpha-, beta-, and gamma-proteobacteria, cyanobacteria, and archaea. The set of genes they regulate is known for 85 out of the 2,353 members of the family. These proteins are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity. The regulatory network in which the family member is involved can be simple, as in TetR (i.e., TetR bound to the target operator represses tetA transcription and is released in the presence of tetracycline), or more complex, involving a series of regulatory cascades in which either the expression of the TetR family member is modulated by another regulator or the TetR family member triggers a cell response to react to environmental insults. Based on what has been learned from the cocrystals of TetR and QacR with their target operators and from their three-dimensional structures in the absence and in the presence of ligands, and based on multialignment analyses of the conserved stretch of 47 amino acids in the 2,353 TetR family members, two groups of residues have been identified. One group includes highly conserved positions involved in the proper orientation of the helix-turn-helix motif and hence seems to play a structural role. The other set of less conserved residues are involved in establishing contacts with the phosphate backbone and target bases in the operator. Information related to the TetR family of regulators has been updated in a database that can be accessed at www.bactregulators.org.
我们已经构建了阻遏蛋白TetR家族蛋白质的通用图谱。最能定义该家族图谱的片段由47个氨基酸残基组成，它们对应于螺旋-转角-螺旋DNA结合基序以及TetR、QacR、CprB和EthR这四个家族成员三维结构中的相邻区域，这四个家族成员的功能和三维结构是已知的。通过用TetR图谱筛选基因组和蛋白质数据库，我们检测到一组属于该家族的2353个非冗余蛋白质。TetR家族的蛋白质已在革兰氏阳性菌、α-、β-和γ-变形菌、蓝细菌和古菌的115个属中被发现。在该家族的2353个成员中，已知有85个成员所调控的基因集。这些蛋白质参与多药外排泵的转录调控、抗生素生物合成途径、对渗透胁迫和有毒化学物质的反应、分解代谢途径的控制、分化过程以及致病性。家族成员所涉及的调控网络可以很简单，如在TetR中（即TetR与靶标操纵子结合会抑制tetA转录，并在四环素存在时释放），也可以更复杂，涉及一系列调控级联反应，其中要么TetR家族成员的表达由另一个调节因子调节，要么TetR家族成员触发细胞反应以应对环境损伤。基于从TetR和QacR与其靶标操纵子的共晶体以及它们在有无配体情况下的三维结构中学到的知识，以及基于对2353个TetR家族成员中47个氨基酸保守片段的多序列比对分析，已鉴定出两组残基。一组包括参与螺旋-转角-螺旋基序正确定向的高度保守位置，因此似乎起结构作用。另一组保守性较低的残基参与与操纵子中的磷酸骨架和靶标碱基建立接触。与TetR调节因子家族相关的信息已在一个数据库中更新，该数据库可在www.bactregulators.org上访问。
