Department of Microbiology and Molecular Genetics and Division of Infectious Diseases, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3773-8. doi: 10.1073/pnas.1018674108. Epub 2011 Feb 14.
The tubulin-like FtsZ protein initiates assembly of the bacterial cytokinetic machinery by polymerizing into a ring structure, the Z ring, at the prospective site of division. To block Z-ring formation over the nucleoid and help coordinate cell division with chromosome segregation, Escherichia coli employs the nucleoid-associated division inhibitor, SlmA. Here, we investigate the mechanism by which SlmA regulates FtsZ assembly. We show that SlmA disassembles FtsZ polymers in vitro. In addition, using chromatin immunoprecipitation (ChIP), we identified 24 SlmA-binding sequences (SBSs) on the chromosome. Remarkably, SlmA binding to SBSs dramatically enhanced its ability to interfere with FtsZ polymerization, and ChIP studies indicate that SlmA regulates FtsZ assembly at these sites in vivo. Because of the dynamic and highly organized nature of the chromosome, coupling SlmA activation to specific DNA binding provides a mechanism for the precise spatiotemporal control of its anti-FtsZ activity within the cell.
类 tubulin 的 FtsZ 蛋白通过聚合形成环结构(Z 环),在分裂的预期位点起始细菌细胞分裂装置的组装。为了阻止核区上 Z 环的形成,并帮助与染色体分离相协调,大肠杆菌利用核区相关的分裂抑制剂 SlmA。在这里,我们研究了 SlmA 调节 FtsZ 组装的机制。我们表明 SlmA 在体外使 FtsZ 聚合物解体。此外,我们通过染色质免疫沉淀(ChIP)鉴定了染色体上的 24 个 SlmA 结合序列(SBS)。值得注意的是,SlmA 与 SBS 的结合极大地增强了其干扰 FtsZ 聚合的能力,ChIP 研究表明 SlmA 在体内在这些位点调节 FtsZ 组装。由于染色体的动态和高度组织化性质,将 SlmA 的激活与特定的 DNA 结合耦合提供了一种机制,用于在细胞内精确地时空控制其抗 FtsZ 活性。