Flipping the switch: dynamic modulation of membrane transporter activity in bacteria.

Flipping the switch: dynamic modulation of membrane transporter activity in bacteria.
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翻转开关:细菌膜转运蛋白活性的动态调节。

DOI:
10.1099/mic.0.001412
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发表时间:
2023-11
期刊:
影响因子:
2.8
通讯作者:
Thomas, Gavin H.
Thomas, Gavin H.
中科院分区:
生物学4区
文献类型:
--
作者:
Elston, Rory;Mulligan, Christopher;Thomas, Gavin H.

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小分子在细菌细胞质膜上的受控进入和驱逐对于有效的细胞生长和细胞稳态至关重要。尽管对编码转运蛋白的基因的转录调节知之甚少,但一旦蛋白质在膜中起作用,这是如何调节转运蛋白活性的知识,这是一种潜在的快速和动态的控制水平。在这篇综述中,我们从细菌运输群落中汇集了文献,这些文献体现了已经发展为快速调节转运蛋白功能的广泛而多样的机制,主要是通过关闭活动来关闭。这包括小分子反馈,与小肽的相互作用抑制,通过结合较大的信号转导蛋白来调节,最后是受控蛋白水解的新兴区域。这些示例中有许多是在金属传输的背景下发现的,金属运输必须很好地平衡对生长必不可少的元素的积极积累,但如果不受细胞内稳态的控制,也可能会迅速变得有毒。与此相一致,这些转运蛋白似乎在多个级别受到调节。最后,我们发现常见的调节主题,通常是通过将其他调节域与转运蛋白融合在一起的,这表明了生物学中转运蛋白活性的广泛调节的潜力。
The controlled entry and expulsion of small molecules across the bacterial cytoplasmic membrane is essential for efficient cell growth and cellular homeostasis. While much is known about the transcriptional regulation of genes encoding transporters, less is understood about how transporter activity is modulated once the protein is functional in the membrane, a potentially more rapid and dynamic level of control. In this review, we bring together literature from the bacterial transport community exemplifying the extensive and diverse mechanisms that have evolved to rapidly modulate transporter function, predominantly by switching activity off. This includes small molecule feedback, inhibition by interaction with small peptides, regulation through binding larger signal transduction proteins and, finally, the emerging area of controlled proteolysis. Many of these examples have been discovered in the context of metal transport, which has to finely balance active accumulation of elements that are essential for growth but can also quickly become toxic if intracellular homeostasis is not tightly controlled. Consistent with this, these transporters appear to be regulated at multiple levels. Finally, we find common regulatory themes, most often through the fusion of additional regulatory domains to transporters, which suggest the potential for even more widespread regulation of transporter activity in biology.
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