Magnesium homeostasis is essential for life and depends on magnesium transporters, whose activity and ion selectivity need to be tightly controlled. Rhomboid intramembrane proteases pervade the prokaryotic kingdom, but their functions are largely elusive. Using proteomics, we find that Bacillus subtilis rhomboid protease YqgP interacts with the membrane-bound ATP-dependent processive metalloprotease FtsH and cleaves MgtE, the major high-affinity magnesium transporter in B. subtilis. MgtE cleavage by YqgP is potentiated in conditions of low magnesium and high manganese or zinc, thereby protecting B. subtilis from Mn2+ /Zn2+ toxicity. The N-terminal cytosolic domain of YqgP binds Mn2+ and Zn2+ ions and facilitates MgtE cleavage. Independently of its intrinsic protease activity, YqgP acts as a substrate adaptor for FtsH, a function that is necessary for degradation of MgtE. YqgP thus unites protease and pseudoprotease function, hinting at the evolutionary origin of rhomboid pseudoproteases such as Derlins that are intimately involved in eukaryotic ER-associated degradation (ERAD). Conceptually, the YqgP-FtsH system we describe here is analogous to a primordial form of "ERAD" in bacteria and exemplifies an ancestral function of rhomboid-superfamily proteins.

中文翻译：

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菱形膜内蛋白酶YqgP许可细菌膜蛋白质量控制作为FtsH AAA蛋白酶的衔接子。

镁稳态对生命至关重要，它取决于镁转运蛋白，镁转运蛋白的活性和离子选择性需要严格控制。菱形膜内蛋白酶遍布原核生物王国，但其功能却难以捉摸。使用蛋白质组学，我们发现枯草芽孢杆菌菱形蛋白酶YqgP与膜结合的ATP依赖性金属蛋白酶FtsH相互作用，并裂解枯草芽孢杆菌中主要的高亲和力镁转运蛋白MgtE。在低镁，高锰或锌的条件下，通过YqgP进行的MgtE裂解会增强，从而保护枯草芽孢杆菌免受Mn2 + / Zn2 +的毒性。YqgP的N端胞质结构域结合Mn2 +和Zn2 +离子并促进MgtE裂解。YqgP与其固有的蛋白酶活性无关，可充当FtsH的底物衔接子，降解MgtE所必需的功能。因此，YqgP结合了蛋白酶和假蛋白酶的功能，暗示了菱形假蛋白酶（例如Derlins）的进化起源，它们直接参与了真核ER相关降解（ERAD）。从概念上讲，我们在此描述的YqgP-FtsH系统类似于细菌中“ ERAD”的原始形式，并代表了菱形超家族蛋白的祖先功能。