Liu, C.（刘冲）, Mao, K., Zhang, M., Sun, Z., Hong, W., Li, C., and Chang, Z., (2008) “The SH3-like Domain Switches Its Interaction Partners to Modulate the Repression Activity of Mycobacterial Iron-dependent Transcription Regulator in Response to Metal Ion Fluctuations” J. Biol. Chem., 283 (4): 2439–2453.

Iron-dependent regulator (IdeR), a metal ion-activated pleiotropic transcription factor, plays a critical role in maintaining the intracellular iron homeostasis in Mycobacteria, which is important for the normal growth of the cells. This study was initially performed in an attempt to elucidate all potential interactions between the various domains of IdeR that occur in living mycobacterial cells. This led to a hitherto unidentified self-association for the SH3-like domain of IdeR. Further studies demonstrate that the SH3-like domain interacts with different partners in the dimeric forms of IdeR depending on the levels of metal ions in the environment: it undergoes inter-subunit self-association in the metal-free DNA-non-binding form, but interacts with the N-terminal domain in the metal-bound DNA binding form in an intra-subunit manner to finely modulate the transcription repression activity of IdeR. Our more detailed mapping studies reveal that the SH3-like domain uses an overlapping surface to participate in these two interactions, which therefore occur in a mutually exclusive fashion. This novel mechanism would allow an effective and cooperative interconversion between the two functional forms of IdeR. Our data also demonstrate that a disturbance of the interactions involving the SH3-like domain impairs the transcription repression activity of IdeR and delays the growth of mycobacterial cells.

中文翻译     

      题目：分支杆菌的铁依赖转录调节蛋白(IdeR)在响应金属离子含量波动时通过切换其类SH3结构域相互作用的对象而调节其转录抑制活性

      摘要：铁依赖转录调节蛋白IdeR是一种被铁离子激活的多效性转录因子，它在维持分支杆菌细胞内的铁离子动态平衡乃至细胞的正常生长过程中发挥着关键性的作用。我们的研究最初是为了揭示在活的分支杆菌细胞内的该蛋白质分子的不同结构域之间发生的所有潜在的相互作用情况。但结果却发现一种还未曾被认识到的 IdeR蛋白质分子的类SH3结构域本身之间可以发生相互作用而维持蛋白质分子的二聚化。进一步的研究表明，IdeR蛋白质分子一直以二聚体形式存在，但在环境中铁离子浓度发生波动时， SH3结构域会与不同的对象结合：在没有铁离子存在时，该蛋白质以非DNA结合形式存在，这时两个亚基之间的类SH3结构域之间发生自相互作用；在有铁离子存在时，该蛋白质以DNA结合形式存在，而这时的SH3结构域却是与同一亚基内的N末端结构域发生相互作用。类SH3结构域在不同条件下发生的这样的相互作用对象的更换能够有效地调节IdeR蛋白质分子的转录抑制活性。我们更为精细的定位研究揭示，类SH3结构域参与的这两种相互作用是通过一个相互重叠的表面而介导的，故以一种相互排它的方式发生。我们发现的这种全新的机制允许IdeR蛋白质分子两种功能形式之间发生有效的和协同性的相互转换。我们的数据还表明，破坏类SH3结构域参与的这些相互作用会减弱IdeR蛋白质分子的转录抑制活性，导致分支杆菌细胞的生长延迟。