Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.
mSphere. 2019 Jan 30;4(1):e00670-18. doi: 10.1128/mSphere.00670-18.
Copper (Cu) is an essential trace element in all organisms, and Cu acquisition during periods of starvation is important for cell survival and proliferation. Although the Cu starvation-responsive transcription factor Mac1 as well as its targeted Cu transporters have been identified in , the molecular mechanisms of Mac1-mediated Cu acquisition have not yet been investigated in We demonstrated that Mac1 and its regulated Cu transporters are required for growth and conidiophore development during Cu starvation in Moreover, Mac1 (AnMac1) showed highly functional conservation with the homolog but not with homologs in and Molecular characterization of Mac1 in demonstrated that the "Cu fist" motif (i.e., residues 1 through 40) harboring Cys, RGHR, and GRP residues is required for the Mac1-mediated low-Cu response but not the Cys-rich motifs REP-I and REP-II. Notably, overexpression of either the CtrA2 Cu transporter or the CtrC Cu transporter individually was unable to functionally rescue the defects in the AnMac1 deletion strain, implying that Cu uptake might require both CtrA2 and CtrC during Cu starvation, which is different from results seen with Findings in this study further suggest that the conserved Mac1-mediated Cu uptake machinery in and is also species specific. Copper is an essential cofactor of enzymes during a variety of biochemical processes. Therefore, Cu acquisition plays critical roles in cell survival and proliferation, especially during Cu starvation. Knowledge of the key motif(s) by which the low-Cu-responsive transcription factor Mac1 senses Cu is important for understanding how Cu uptake is controlled. Findings in this study demonstrated that the Cu fist motif, but not Cys-rich motifs, is essential for Mac1-mediated Cu uptake in In addition, Cu transporters CtrA2 and CtrC are both required for Mac1-mediated Cu uptake during Cu starvation in , indicating that species-specific machinery exists for Cu acquisition in .
铜（Cu）是所有生物的必需微量元素，在饥饿期间获取 Cu 对于细胞存活和增殖很重要。尽管已经在 中鉴定了铜饥饿反应转录因子 Mac1 及其靶向的 Cu 转运蛋白，但 Mac1 介导的 Cu 获取的分子机制尚未在 中研究。我们证明，在 Cu 饥饿期间，Mac1 及其调节的 Cu 转运蛋白对于 的生长和分生孢子梗发育是必需的。此外， Mac1（AnMac1）与 的同源物表现出高度的功能保守性，但与 和 的同源物没有保守性。Mac1 在 中的分子特征表明，含有半胱氨酸、RGHR 和 GRP 残基的“Cu 拳头”基序（即残基 1 到 40）对于 Mac1 介导的低 Cu 反应是必需的，但对于富含半胱氨酸的 REP-I 和 REP-II 基序不是必需的。值得注意的是，单独过表达 CtrA2 Cu 转运蛋白或 CtrC Cu 转运蛋白都不能在功能上挽救 AnMac1 缺失菌株的缺陷，这表明在 Cu 饥饿期间，Cu 摄取可能需要 CtrA2 和 CtrC，这与 中的结果不同。本研究的结果进一步表明， 和 中保守的 Mac1 介导的 Cu 摄取机制也是种特异性的。铜是各种生化过程中酶的必需辅助因子。因此，Cu 获取在细胞存活和增殖中起着关键作用，尤其是在 Cu 饥饿期间。了解低 Cu 反应转录因子 Mac1 感知 Cu 的关键基序对于理解 Cu 摄取如何受到控制非常重要。本研究的结果表明，Cu 拳头基序，而不是富含半胱氨酸的基序，对于 中 Mac1 介导的 Cu 摄取是必需的。此外，Cu 转运蛋白 CtrA2 和 CtrC 在 中 Cu 饥饿期间都是 Mac1 介导的 Cu 摄取所必需的，这表明在 Cu 获取中存在种特异性机制。
