Metallochaperones and metalloregulation in bacteria.

Metallochaperones and metalloregulation in bacteria.
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DOI:
10.1042/ebc20160076
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发表时间:
2017-05-09
影响因子:
6.4
通讯作者:
Giedroc DP
Giedroc DP
中科院分区:
生物学2区
文献类型:
--
作者:
Capdevila DA;Edmonds KA;Giedroc DP

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细菌过渡金属内稳态,或简称为“金属稳态”,描述了细胞控制从锰(Mn)到锌(Zn)等功能所需金属辅因子在细胞内的可利用性的过程,避免金属缺乏和毒性。金属稳态是脊椎动物宿主 - 病原体界面的一个新兴方面,其特征是对生物必需金属的“拔河”,并为该领域近期的许多工作提供了动力。宿主采用多种策略使微生物病原体缺乏必需金属,而对于其他一些金属,则试图利用具有高度竞争性的金属来限制细菌感染。细菌必须能够适应这些改变过渡金属环境的作用,并利用高度特化的金属感应转录调节因子(称为金属调节蛋白)和金属伴侣蛋白,将金属分配到特定部位,以介导这种适应性反应。在本文中,我们讨论了在理解这种适应性反应的结构机制和金属特异性方面的最新进展,重点关注在金属酶和金属传感器中的金属辅因子活性位点组装中起作用的需能金属伴侣蛋白,它们调控着对金属限制和中毒的系统级反应。
Bacterial transition metal homoeostasis or simply ‘metallostasis’ describes the process by which cells control the intracellular availability of functionally required metal cofactors, from manganese (Mn) to zinc (Zn), avoiding bothmetal deprivation and toxicity. Metallostasis is an emerging aspect of the vertebrate host–pathogen interface that is defined by a ‘tug-of-war’ for biologically essential metals and provides the motivation for much recent work in this area. The host employs a number of strategies to starve the microbial pathogen of essential metals, while for others attempts to limit bacterial infections by leveraging highly competitive metals. Bacteria must be capable of adapting to these efforts to remodel the transition metal landscape and employ highly specialized metal sensing transcriptional regulators, termed metalloregulatory proteins, and metallochaperones, that allocate metals to specific destinations, to mediate this adaptive response. In this essay, we discuss recent progress in our understanding of the structural mechanisms and metal specificity of this adaptive response, focusing on energy-requiring metallochaperones that play roles in the metallocofactor active site assembly in metalloenzymes and metallosensors, which govern the systems-level response to metal limitation and intoxication.