Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.
VIB-KU Leuven Center for Microbiology, Leuven, Belgium.
Nat Commun. 2024 Nov 8;15(1):9684. doi: 10.1038/s41467-024-53980-1.
During growth, cells need to synthesize and expand their envelope, a process that requires careful regulation. Here, we show that the GTPase ObgE of E. coli contributes to the regulation of lipopolysaccharide (LPS) synthesis, an essential component of the Gram-negative outer membrane. Using a dominant-negative mutant (named 'ObgE*'), we show a direct interaction between ObgE and LpxA, which catalyzes the first step in LPS synthesis. This interaction is enhanced by the mutation in ObgE* which, when bound to GTP, leads to inhibition of LpxA, decreased LPS synthesis, and cell death. Although wild-type ObgE does not exert the same strong effects as ObgE* on LpxA or LPS synthesis, our data indicate that ObgE participates in the regulation of cell envelope synthesis in E. coli. Because ObgE also influences other cellular functions (i.e., ribosome assembly, DNA replication, etc.), it seems increasingly plausible that this GTPase coordinates several processes to finetune cell growth.
在生长过程中,细胞需要合成和扩展其包膜,这是一个需要仔细调节的过程。在这里,我们表明大肠杆菌的 GTPase ObgE 有助于调节脂多糖 (LPS) 的合成,LPS 是革兰氏阴性外膜的重要组成部分。使用显性负突变体(命名为 'ObgE*'),我们显示 ObgE 与催化 LPS 合成第一步的 LpxA 之间存在直接相互作用。这种相互作用通过 ObgE中的突变得到增强,当 ObgE结合 GTP 时,会抑制 LpxA,减少 LPS 合成并导致细胞死亡。尽管野生型 ObgE 对 LpxA 或 LPS 合成没有 ObgE*那样强烈的影响,但我们的数据表明 ObgE 参与了大肠杆菌细胞包膜合成的调节。由于 ObgE 还会影响其他细胞功能(核糖体组装、DNA 复制等),因此这种 GTPase 似乎越来越有可能协调多个过程来微调细胞生长。