Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas, Houston, Texas, USA.
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas, Houston, Texas, USA
J Bacteriol. 2019 Jan 28;201(4). doi: 10.1128/JB.00579-18. Print 2019 Feb 15.
The initiation of cell division requires three proteins, FtsZ, FtsA, and ZipA, which assemble in a dynamic ring-like structure at midcell. Along with the transmembrane protein ZipA, the actin-like FtsA helps to tether treadmilling polymers of tubulin-like FtsZ to the membrane. In addition to forming homo-oligomers, FtsA and ZipA interact directly with the C-terminal conserved domain of FtsZ. Gain-of-function mutants of FtsA are deficient in forming oligomers and can bypass the need for ZipA, suggesting that ZipA may normally function to disrupt FtsA oligomers, although no direct interaction between FtsA and ZipA has been reported. Here, we use cross-linking to show that FtsA and ZipA indeed interact directly. We identify the exposed surface of FtsA helix 7, which also participates in binding to ATP through its internal surface, as a key interface needed for the interaction with ZipA. This interaction suggests that FtsZ's membrane tethers may regulate each other's activities. To divide, most bacteria first construct a protein machine at the plane of division and then recruit the machinery that will synthesize the division septum. In , this first stage involves the assembly of FtsZ polymers at midcell, which directly bind to membrane-associated proteins FtsA and ZipA to form a discontinuous ring structure. Although FtsZ directly binds both FtsA and ZipA, it is unclear why FtsZ requires two separate membrane tethers. Here, we uncover a new direct interaction between the tethers, which involves a helix within FtsA that is adjacent to its ATP binding pocket. Our findings imply that in addition to their known roles as FtsZ membrane anchors, FtsA and ZipA may regulate each other's structure and function.
细胞分裂的启动需要三种蛋白质，FtsZ、FtsA 和 ZipA，它们在细胞中部组装成一个动态的环状结构。与跨膜蛋白 ZipA 一起，肌动蛋白样 FtsA 有助于将微管样 FtsZ 的 treadmilling 聚合物连接到膜上。除了形成同源寡聚体外，FtsA 和 ZipA 还直接与 FtsZ 的 C 端保守结构域相互作用。FtsA 的功能获得突变体在形成寡聚体方面存在缺陷，并且可以绕过对 ZipA 的需求，这表明 ZipA 可能通常通过破坏 FtsA 寡聚体来发挥作用，尽管尚未报道 FtsA 和 ZipA 之间存在直接相互作用。在这里，我们使用交联实验证明 FtsA 和 ZipA 确实直接相互作用。我们确定了 FtsA 螺旋 7 的暴露表面，该表面也通过其内部表面参与与 ATP 的结合，这是与 ZipA 相互作用所需的关键界面。这种相互作用表明，FtsZ 的膜连接物可能调节彼此的活性。为了进行分裂，大多数细菌首先在分裂平面上构建一个蛋白质机器，然后招募将合成分裂隔膜的机器。在这方面，第一阶段涉及 FtsZ 聚合物在细胞中部的组装，该聚合物直接与膜相关蛋白 FtsA 和 ZipA 结合形成不连续的环结构。尽管 FtsZ 直接与 FtsA 和 ZipA 结合，但不清楚为什么 FtsZ 需要两个独立的膜连接物。在这里，我们揭示了连接物之间的一个新的直接相互作用，该相互作用涉及 FtsA 中的一个螺旋，该螺旋紧邻其 ATP 结合口袋。我们的发现表明，除了作为 FtsZ 膜锚的已知作用外，FtsA 和 ZipA 可能还调节彼此的结构和功能。
