Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx
Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx
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DOI：
10.1016/j.str.2019.03.009
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发表时间：
2019-06-04
期刊：
影响因子：
5.7
通讯作者：
von Wachenfeldt, Claes
中科院分区：
文献类型：
--
作者：
Awad, Wael;Al-Eryani, Yusra;von Wachenfeldt, Claes
YjbH是ClpXP蛋白酶对RNA聚合酶结合转录因子Spx进行有效蛋白水解所需的细菌衔接蛋白。我们报告的结构YjbH在复杂的Spx。YjbH包含DsbA样硫氧还蛋白结构域，其通过接头连接至C-末端结构域，使人联想到有翼螺旋-转角-螺旋折叠。YjbH和Spx之间的相互作用涉及大的表面积。与YjbH的结合使Spx的C-末端ClpX识别区稳定。我们发现，突变的关键YjbH接触残基废除Spx识别。小角X射线散射和氢-氘交换质谱分析确定了溶液中存在稳定的异二聚体复合物，并提供了证据表明Spx与YjbH的结合降低了Spx的整体构象灵活性。我们的研究结果提供了深入了解Spx识别的分子基础，并提出了一个模型，YjbH如何稳定Spx和显示C末端的Spx参与ClpXP。
YjbH is a bacterial adaptor protein required for efficient proteolysis of the RNA polymerase-binding transcription factor Spx by the ClpXP protease. We report the structure of YjbH in complex with Spx. YjbH comprises a DsbA-like thioredoxin domain connected via a linker to a C-terminal domain reminiscent of the winged helix-turn-helix fold. The interaction between YjbH and Spx involves a large surface area. Binding to YjbH stabilizes the C-terminal ClpX recognition region of Spx. We show that mutation of critical YjbH contact residues abrogates Spx recognition. Small-angle X-ray scattering and hydrogen-deuterium exchange mass spectrometry analyses determined the existence of a stable heterodimeric complex in solution and provide evidence that binding of Spx to YjbH reduces the overall conformational flexibility of Spx. Our findings provide insights into the molecular basis for Spx recognition and suggest a model for how YjbH stabilizes Spx and displays the C terminus of Spx for engagement by ClpXP.