Roy Tanaya Basu, Sarma Siddhartha P
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India.
Proteins. 2025 Jan;93(1):176-196. doi: 10.1002/prot.26589. Epub 2023 Sep 22.
The present study endeavors to decode the details of the transcriptional autoregulation effected by the MazE9 antitoxin of the Mycobacterium tuberculosis MazEF9 toxin-antitoxin system. Regulation of this bicistronic operon at the level of transcription is a critical biochemical process that is key for the organism's stress adaptation and virulence. Here, we have reported the solution structure of the DNA binding domain of MazE9 and scrutinized the thermodynamic and kinetic parameters operational in its interaction with the promoter/operator region, specific to the mazEF9 operon. A HADDOCK model of MazE9 bound to its operator DNA has been calculated based on the information on interacting residues obtained from these studies. The thermodynamics and kinetics of the interaction of MazE9 with the functionally related mazEF6 operon indicate that the potential for intracellular cross-regulation is unlikely. An interesting feature of MazE9 is the cis ⇌ trans conformational isomerization of proline residues in the intrinsically disordered C-terminal domain of this antitoxin.
本研究致力于解析结核分枝杆菌MazEF9毒素-抗毒素系统中的抗毒素MazE9所实现的转录自调控细节。在转录水平对这个双顺反子操纵子的调控是一个关键的生化过程，对生物体的应激适应和毒力至关重要。在此，我们报道了MazE9的DNA结合结构域的溶液结构，并详细研究了其与mazEF9操纵子特有的启动子/操纵子区域相互作用时的热力学和动力学参数。基于这些研究获得的关于相互作用残基的信息，计算出了MazE9与其操纵子DNA结合的HADDOCK模型。MazE9与功能相关的mazEF6操纵子相互作用的热力学和动力学表明，细胞内交叉调控的可能性不大。MazE9的一个有趣特征是，在这种抗毒素的内在无序C末端结构域中，脯氨酸残基存在顺式⇌反式构象异构化。
