CorE from Myxococcus xanthus is a copper-dependent RNA polymerase sigma factor.
CorE from Myxococcus xanthus is a copper-dependent RNA polymerase sigma factor.
复制标题
DOI：
10.1371/journal.pgen.1002106
复制
发表时间：
2011-06
期刊：
影响因子：
4.5
通讯作者：
Muñoz-Dorado J
中科院分区：
文献类型：
--
作者：
Gómez-Santos N;Pérez J;Sánchez-Sutil MC;Moraleda-Muñoz A;Muñoz-Dorado J
铜的双重毒性/重要性迫使细胞在所有生物体中（从细菌到人类）保持这种金属的严格调节的稳态。因此，许多基因先前已被报道参与细菌中的铜解毒。粘球菌xanthus，原核生物，编码许多蛋白质参与铜的稳态，差异调节这种金属。已发现ECF（细胞质外功能）家族的σ因子CorE调节多铜氧化酶cuoB、P1 B型ATP酶copA和copB以及编码具有重金属相关结构域的蛋白质的基因的表达。对CorE的表征表明，它需要铜在体外结合DNA。由CorE调控的基因表现出特征性的表达谱，在添加铜后2 h达到峰值。此后表达迅速下降到基础水平，尽管金属仍然存在于培养基中，表明CorE的活性受到激活和失活过程的调节。使用一价和二价金属分别模拟Cu（I）和Cu（II），以及使用有利于形成该金属的两种氧化还原态的添加剂，已经揭示了CorE被Cu（II）活化而被Cu（I）失活。CorE的激活/失活特性存在于位于蛋白质C末端的富含Cys的结构域中。在这些残基的点突变，允许几个Cys参与的激活和失活的核心鉴定。基于这些数据，沿着比较基因组研究，提出了一组新的ECF σ因子，其不仅在机制上明显不同于迄今为止表征的其他σ因子，而且也不同于其他金属调节剂。铜对生物体有双重作用。它对生命至关重要，但过量会引起细胞损伤，迫使细胞维持这种金属的调节稳态。铜的这两种拮抗性生物学效应分别由两种人类遗传疾病Menkes综合征和Wilson病清楚地说明，这两种疾病分别由这种金属的缺乏或积累引起。粘球菌xanthus，一种土壤细菌，也必须科普环境中铜浓度的变化。这种粘细菌的大基因组编码许多参与铜稳态的基因，所有这些基因都受到差异调节，表明许多调节剂参与这种原核生物中的铜稳态。在这里，我们确定了这些监管机构之一（核心），这属于家庭的细胞质外功能（ECF）σ因子。我们证明，核心代表了一个新的组ECF σ因子和金属调节剂，因为它的活性是由铜的氧化还原状态调制。这种能力存在于富含Cys的结构域中，该结构域也已在不同细菌门的其他σ因子中发现。因此，我们建议，CorE是一个新的ECF σ因子的机制组的第一个成员。
The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many proteins involved in copper homeostasis that are differentially regulated by this metal. A σ factor of the ECF (extracytoplasmic function) family, CorE, has been found to regulate the expression of the multicopper oxidase cuoB, the P1B-type ATPases copA and copB, and a gene encoding a protein with a heavy-metal-associated domain. Characterization of CorE has revealed that it requires copper to bind DNA in vitro. Genes regulated by CorE exhibit a characteristic expression profile, with a peak at 2 h after copper addition. Expression rapidly decreases thereafter to basal levels, although the metal is still present in the medium, indicating that the activity of CorE is modulated by a process of activation and inactivation. The use of monovalent and divalent metals to mimic Cu(I) and Cu(II), respectively, and of additives that favor the formation of the two redox states of this metal, has revealed that CorE is activated by Cu(II) and inactivated by Cu(I). The activation/inactivation properties of CorE reside in a Cys-rich domain located at the C terminus of the protein. Point mutations at these residues have allowed the identification of several Cys involved in the activation and inactivation of CorE. Based on these data, along with comparative genomic studies, a new group of ECF σ factors is proposed, which not only clearly differs mechanistically from the other σ factors so far characterized, but also from other metal regulators. Copper exerts a dual effect on living organisms. It is essential for life, but an excess provokes cell damage, forcing cells to maintain a regulated homeostasis for this metal. These two antagonistic biological effects of copper are clearly illustrated by two human genetic disorders, Menkes syndrome and Wilson disease, caused by deficiency or accumulation of this metal, respectively. Myxococcus xanthus, a soil-dwelling bacterium, also has to cope with changes in copper concentration in its environment. The large genome of this myxobacterium encodes many genes involved in copper homeostasis, all of which are differentially regulated, indicating that many regulators participate in copper homeostasis in this prokaryote. Here, we identify one of these regulators (CorE), which belongs to the family of the extracytoplasmic function (ECF) σ factors. We demonstrate that CorE represents a novel group of ECF σ factors and of metal regulators, because its activity is modulated by the redox state of copper. This ability resides in a Cys-rich domain, which has also been found in other σ factors of different bacterial phyla. Therefore, we propose that CorE is the first member of a mechanistically new group of ECF σ factors.
登录
查看更多内容
影响因子：
3.6
作者：
Cho, KY;Zusman, DR
通讯作者：
Zusman, DR
影响因子：
3.2
作者：
MARTINEZCANAMERO, M;MUNOZDORADO, J;INOUYE, S
通讯作者：
INOUYE, S
影响因子：
16
作者：
Campbell, Elizabeth A.;Greenwell, Roger;Darst, Seth A.
通讯作者：
Darst, Seth A.
影响因子：
5.8
作者：
Münch, R;Hiller, K;Jahn, D
通讯作者：
Jahn, D
影响因子：
13.8
作者：
Cooper, CE;Patel, RP;Darley-Usmar, VM
通讯作者：
Darley-Usmar, VM