镍依赖基因表达转录因子SrnR的结构、动力学和功能。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Metallomics Pub Date : 2021-12-20 DOI:10.1093/mtomcs/mfab069
Luca Mazzei, Francesco Musiani, Szymon Żerko, Wiktor Koźminski, Michele Cianci, Ylenia Beniamino, Stefano Ciurli, Barbara Zambelli
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引用次数: 2

摘要

灰色链霉菌(Streptomyces griseus)是一种生产抗菌药物的细菌,在植物修复中有可能应用,它表达两种金属依赖性超氧化物歧化酶(SOD)酶,其活性位点含有Fe(II)或Ni(II)。特别是,这两种蛋白的交替表达以金属依赖模式发生,在高细胞内Ni(II)浓度下,双组分系统(TCS)抑制了Fe(II)酶基因(sodF)。该复合物涉及两个蛋白,即SgSrnR和SgSrnQ,它们分别代表系统的转录调节因子和Ni(II)传感器。SgSrnR属于金属依赖性转录因子ArsR/SmtB家族;在载脂蛋白形式和缺乏SgSrnQ的情况下,它可以结合sodF的DNA操作符,上调基因转录。根据最近提出的假设,Ni(II)结合SgSrnQ会促进其与SgSrnR的相互作用,导致复合物从DNA中释放,从而下调sof的表达。据预测,SgSrnQ是高度无序的,因此,在分子水平上理解SgSrnR/SgSrnQ TCS如何特异性响应Ni(II)需要了解SgSrnR的结构、动态和功能特征。研究人员利用x射线晶体学、核磁共振(NMR)光谱学、原子分子动力学计算、等温滴定量热法和硅分子对接等方法进行了协同研究。结果表明,同源二聚体载脂蛋白- sgsrnr通过两步过程与其操作子结合,该过程涉及蛋白质的更刚性的球形部分,并使其大部分无序区域在镍依赖过程中可能与无序的SgSrnQ相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Structure, dynamics, and function of SrnR, a transcription factor for nickel-dependent gene expression.

Streptomyces griseus, a bacterium producing antibacterial drugs and featuring possible application in phytoremediation, expresses two metal-dependent superoxide dismutase (SOD) enzymes, containing either Fe(II) or Ni(II) in their active site. In particular, the alternative expression of the two proteins occurs in a metal-dependent mode, with the Fe(II)-enzyme gene (sodF) repressed at high intracellular Ni(II) concentrations by a two-component system (TCS). This complex involves two proteins, namely SgSrnR and SgSrnQ, which represent the transcriptional regulator and the Ni(II) sensor of the system, respectively. SgSrnR belongs to the ArsR/SmtB family of metal-dependent transcription factors; in the apo-form and in the absence of SgSrnQ, it can bind the DNA operator of sodF, upregulating gene transcription. According to a recently proposed hypothesis, Ni(II) binding to SgSrnQ would promote its interaction with SgSrnR, causing the release of the complex from DNA and the consequent downregulation of the sodF expression. SgSrnQ is predicted to be highly disordered, thus the understanding, at the molecular level, of how the SgSrnR/SgSrnQ TCS specifically responds to Ni(II) requires the knowledge of the structural, dynamic, and functional features of SgSrnR. These were investigated synergistically in this work using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, atomistic molecular dynamics calculations, isothermal titration calorimetry, and in silico molecular docking. The results reveal that the homodimeric apo-SgSrnR binds to its operator in a two-step process that involves the more rigid globular portion of the protein and leaves its largely disordered regions available to possibly interact with the disordered SgSrnQ in a Ni-dependent process.

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来源期刊
Metallomics
Metallomics 生物-生化与分子生物学
CiteScore
7.00
自引率
5.90%
发文量
87
审稿时长
1 months
期刊介绍: Global approaches to metals in the biosciences
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