A bacterial secretosome for regulated envelope biogenesis and quality control?
A bacterial secretosome for regulated envelope biogenesis and quality control?
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DOI：
10.1099/mic.0.001255
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发表时间：
2022-10-01
期刊：
影响因子：
2.8
通讯作者：
Collinson，Ian
中科院分区：
文献类型：
--
作者：
Watkins，Daniel W.;Williams，Sophie L.;Collinson，Ian
革兰氏阴性菌包膜是抵御环境压力和抗生素的第一道防线。因此，其生物发生是相当重要的根本利益，也是解决日益严重的抗微生物药物耐药性问题的挑战。所有的细菌蛋白质都是在细胞质中合成的，所以内外膜蛋白和质周蛋白必须通过专门的蛋白质机器运送到它们的最终目的地。Sec易位子是一种普遍存在的整体内膜（IM）复合体，是这一过程的关键，是蛋白质从细胞质转运到细胞包膜的主要通道；这可以在翻译过程中或之后实现。蛋白质需要被引导到膜内（通常是共翻译），否则SecA利用ATP和质子动力（PMF）驱动蛋白质在翻译后穿过膜。然后，这些蛋白质被伴侣蛋白拾取，在周质中折叠，或者被运送到β桶组装机器（BAM）中，以整合到外膜中。核心的异三聚体secyeg复合物形成了一个广泛的相互作用网络的枢纽，调节蛋白质的传递和质量控制。在这里，我们对这种“分泌体”进行了生化探索，这是一种非常大的、通用的、可互换的组装，其核心是sec易位；具有促进分泌（SecDF）、内膜和外膜蛋白插入（分别为YidC和BAM）、蛋白质折叠和质量控制（如PpiD、YfgM和FtsH）的相互作用。我们提出这些因素和其他因素之间的动态相互作用，以确保有效的包膜生物发生，调节以适应细胞伸长和分裂的要求。我们相信这种组织对细胞壁的生物发生和重塑至关重要，因此对其进行扰动可能是开发抗微生物药物的一种手段。
The Gram-negative bacterial envelope is the first line of defence against environmental stress and antibiotics. Therefore, its biogenesis is of considerable fundamental interest, as well as a challenge to address the growing problem of antimicrobial resistance. All bacterial proteins are synthesised in the cytosol, so inner- and outer-membrane proteins, and periplasmic residents have to be transported to their final destinations via specialised protein machinery. The Sec translocon, a ubiquitous integral inner-membrane (IM) complex, is key to this process as the major gateway for protein transit from the cytosol to the cell envelope; this can be achieved during their translation, or afterwards. Proteins need to be directed into the inner-membrane (usually co-translational), otherwise SecA utilises ATP and the proton-motive-force (PMF) to drive proteins across the membrane post-translationally. These proteins are then picked up by chaperones for folding in the periplasm, or delivered to the β-barrel assembly machinery (BAM) for incorporation into the outer-membrane. The core hetero-trimeric SecYEG-complex forms the hub for an extensive network of interactions that regulate protein delivery and quality control. Here, we conduct a biochemical exploration of this ‘secretosome’ –a very large, versatile and inter-changeable assembly with the Sec-translocon at its core; featuring interactions that facilitate secretion (SecDF), inner- and outer-membrane protein insertion (respectively, YidC and BAM), protein folding and quality control (e.g. PpiD, YfgM and FtsH). We propose the dynamic interplay amongst these, and other factors, act to ensure efficient envelope biogenesis, regulated to accommodate the requirements of cell elongation and division. We believe this organisation is critical for cell wall biogenesis and remodelling and thus its perturbation could be a means for the development of anti-microbials.