Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
Chemical Biology and Molecular Biophysics program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan.
Nat Commun. 2023 Apr 5;14(1):1903. doi: 10.1038/s41467-023-37543-4.
The synthesis of the cell-wall peptidoglycan during bacterial cell division is mediated by a multiprotein machine, called the divisome. The essential membrane protein complex of FtsB, FtsL and FtsQ (FtsBLQ) is at the heart of the divisome assembly cascade in Escherichia coli. This complex regulates the transglycosylation and transpeptidation activities of the FtsW-FtsI complex and PBP1b via coordination with FtsN, the trigger for the onset of constriction. Yet the underlying mechanism of FtsBLQ-mediated regulation is largely unknown. Here, we report the full-length structure of the heterotrimeric FtsBLQ complex, which reveals a V-shaped architecture in a tilted orientation. Such a conformation could be strengthened by the transmembrane and the coiled-coil domains of the FtsBL heterodimer, as well as an extended β-sheet of the C-terminal interaction site involving all three proteins. This trimeric structure may also facilitate interactions with other divisome proteins in an allosteric manner. These results lead us to propose a structure-based model that delineates the mechanism of the regulation of peptidoglycan synthases by the FtsBLQ complex.
细菌细胞分裂过程中，细胞壁肽聚糖的合成是由一种叫做分裂装置的多蛋白机器介导的。在大肠杆菌中，FtsB、FtsL 和 FtsQ（FtsBLQ）的必需膜蛋白复合物是分裂装置组装级联的核心。该复合物通过与引发收缩的触发蛋白 FtsN 的协调，调节 FtsW-FtsI 复合物和 PBP1b 的转糖基化和转肽作用。然而，FtsBLQ 介导的调节的潜在机制在很大程度上仍是未知的。在这里，我们报告了异源三聚体 FtsBLQ 复合物的全长结构，该结构呈现出倾斜取向的 V 形架构。这种构象可以通过 FtsBL 异二聚体的跨膜和卷曲螺旋结构域以及涉及所有三个蛋白质的 C 末端相互作用位点的扩展β-折叠得到加强。这种三聚体结构还可能以别构的方式促进与其他分裂装置蛋白的相互作用。这些结果使我们提出了一个基于结构的模型，该模型描绘了 FtsBLQ 复合物对肽聚糖合成酶的调节机制。
