Szymczak Justyna, Strzałka Agnieszka, Bania Dominik, Jakimowicz Dagmara, Szafran Marcin Jan
Department of Molecular Microbiology, Faculty of Biotechnology, University of Wrocław, 50-231 Wrocław, Poland.
Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf623.
The segregation of bacterial chromosomes is widely mediated by partitioning proteins (ParAB). While ParB binds DNA specifically by recognizing short, palindromic sequences known as parS sites, ParA utilizes its ATPase activity to generate the force to translocate ParB-DNA nucleoprotein complexes (segrosomes). The assembly of the segrosome requires the association of ParB with parS, followed by nonspecific spread of the protein along the DNA. To spread on DNA, the ParB dimer must entrap the parS site within the complex, a process triggered by CTP binding to the conserved GERR amino acid motif. In Streptomyces, a genus of soil-dwelling, multigenomic bacteria that have a complex life cycle, ParB-dependent chromosome partitioning is initiated during the growth of sporogenic hyphae. However, the molecular mechanisms underlying segrosome formation in Streptomyces and their ability to coordinate with sporogenic development remain incompletely understood. In this study, we advance the understanding of chromosome segregation in bacteria by exploring the effects of CTP binding and hydrolysis on the formation of the partitioning complex in Streptomyces coelicolor. Here, via in vitro approaches, we demonstrate that a conserved GERR motif is essential for CTP binding and hydrolysis by S. coelicolor ParB. Moreover, the motif is crucial for CTP-dependent ParB accumulation on DNA. Using mutant strains, we show the significance of the GERR motif for segrosome complex assembly. Additionally, we provide data showing that the CTP-binding motif contributes to the regulation of the growth of sporogenic cells. Overall, we show that CTP-dependent segrosome assembly impacts the development of S. coelicolor sporogenic cells.
细菌染色体的分离广泛由分区蛋白(ParAB)介导。虽然ParB通过识别称为parS位点的短回文序列特异性结合DNA,但ParA利用其ATP酶活性产生力量来转运ParB-DNA核蛋白复合物(分离体)。分离体的组装需要ParB与parS结合,随后蛋白质沿DNA进行非特异性扩散。为了在DNA上扩散,ParB二聚体必须将parS位点捕获在复合物中,这一过程由CTP与保守的GERR氨基酸基序结合触发。在链霉菌属中,这是一类生活在土壤中的多基因组细菌,具有复杂的生命周期,ParB依赖性染色体分离在产孢菌丝生长期间启动。然而,链霉菌中分离体形成的分子机制及其与产孢发育协调的能力仍未完全了解。在这项研究中,我们通过探索CTP结合和水解对天蓝色链霉菌中分区复合物形成的影响,推进了对细菌染色体分离的理解。在这里,通过体外方法,我们证明保守的GERR基序对于天蓝色链霉菌ParB的CTP结合和水解至关重要。此外,该基序对于CTP依赖性ParB在DNA上的积累至关重要。使用突变菌株,我们展示了GERR基序对于分离体复合物组装的重要性。此外,我们提供的数据表明CTP结合基序有助于调节产孢细胞的生长。总体而言,我们表明CTP依赖性分离体组装影响天蓝色链霉菌产孢细胞的发育。