Department of Bacterial Genetics, Faculty of Biology, Institute of Microbiology, University of Warsaw, 02-096 Warsaw, Poland.
Laboratory of Structural Bioinformatics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
Int J Mol Sci. 2021 Dec 15;22(24):13451. doi: 10.3390/ijms222413451.
The bacterial proteins of the Dsb family catalyze the formation of disulfide bridges between cysteine residues that stabilize protein structures and ensure their proper functioning. Here, we report the detailed analysis of the Dsb pathway of . The oxidizing Dsb system of this pathogen is unique because it consists of two monomeric DsbAs (DsbA1 and DsbA2) and one dimeric bifunctional protein (C8J_1298). Previously, we showed that DsbA1 and C8J_1298 are redundant. Here, we unraveled the interaction between the two monomeric DsbAs by in vitro and in vivo experiments and by solving their structures and found that both monomeric DsbAs are dispensable proteins. Their structures confirmed that they are homologs of EcDsbL. The slight differences seen in the surface charge of the proteins do not affect the interaction with their redox partner. Comparative proteomics showed that several respiratory proteins, as well as periplasmic transport proteins, are targets of the Dsb system. Some of these, both donors and electron acceptors, are essential elements of the respiratory process under oxygen-limiting conditions in the host intestine. The data presented provide detailed information on the function of the Dsb system, identifying it as a potential target for novel antibacterial molecules.
Dsb 家族的细菌蛋白催化半胱氨酸残基之间形成二硫键，稳定蛋白质结构并确保其正常功能。在这里，我们报告了 的 Dsb 途径的详细分析。该病原体的氧化 Dsb 系统是独特的，因为它由两个单体 DsbAs（DsbA1 和 DsbA2）和一个二聚体双功能蛋白（C8J_1298）组成。以前，我们表明 DsbA1 和 C8J_1298 是冗余的。在这里，我们通过体外和体内实验以及解决它们的结构揭示了两个单体 DsbAs 之间的相互作用，并发现这两种单体 DsbAs 都是可有可无的蛋白质。它们的结构证实它们是 EcDsbL 的同源物。蛋白质表面电荷上的细微差异不会影响与它们的氧化还原伴侣的相互作用。比较蛋白质组学表明，几种呼吸蛋白以及周质转运蛋白是 Dsb 系统的靶标。其中一些，既是供体又是电子受体，是宿主肠道内缺氧条件下 呼吸过程的重要组成部分。所提供的数据提供了有关 Dsb 系统功能的详细信息，将其确定为新型抗菌分子的潜在靶标。
