The coiled-coil domain of Escherichia coli FtsLB is a structurally detuned element critical for modulating its activation in bacterial cell division.
The coiled-coil domain of Escherichia coli FtsLB is a structurally detuned element critical for modulating its activation in bacterial cell division.
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DOI：
10.1016/j.jbc.2021.101460
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Senes A
中科院分区：
文献类型：
--
作者：
Craven SJ;Condon SGF;Díaz Vázquez G;Cui Q;Senes A
FtsLB复合物是细菌细胞分裂的关键调节剂，以关闭状态或打开状态存在，其支持间隔肽聚糖合成的激活。在大肠杆菌中，已知对这种激活至关重要的残基位于FtsLB的周质卷曲螺旋结构域的C-末端附近的区域，这引起了关于这种保守结构域在激活机制中的确切作用的问题。在这里，我们研究了FtsLB卷曲螺旋核心内发现的一组不寻常的极性氨基酸。我们假设这些氨基酸可能降低结构域的结构稳定性，因此可能对控制构象变化很重要。我们发现，突变这些位置的疏水残基增加了FtsLB的热稳定性，但引起细胞分裂缺陷，这表明卷曲螺旋结构域是一个“失谐”的结构元素。此外，我们确定了极性簇内的抑制突变，表明极性氨基酸的精确身份对于微调关闭和打开状态之间的结构平衡是重要的。我们提出了一个修订的结构模型的四聚体FtsLB（命名为“Y-模型”），其中周质域分裂成一对卷曲螺旋分支。在这种构型中，极性氨基酸的亲水性末端部分保持比在原始四螺旋束模型（“I-模型”）中更有利地暴露于水。我们建议，这种结构的转变，依赖于其边缘的稳定性，参与激活FtsLB复合物和触发间隔细胞壁重建。
The FtsLB complex is a key regulator of bacterial cell division, existing in either an off state or an on state, which supports the activation of septal peptidoglycan synthesis. In Escherichia coli, residues known to be critical for this activation are located in a region near the C-terminal end of the periplasmic coiled-coil domain of FtsLB, raising questions about the precise role of this conserved domain in the activation mechanism. Here, we investigate an unusual cluster of polar amino acids found within the core of the FtsLB coiled coil. We hypothesized that these amino acids likely reduce the structural stability of the domain and thus may be important for governing conformational changes. We found that mutating these positions to hydrophobic residues increased the thermal stability of FtsLB but caused cell division defects, suggesting that the coiled-coil domain is a “detuned” structural element. In addition, we identified suppressor mutations within the polar cluster, indicating that the precise identity of the polar amino acids is important for fine-tuning the structural balance between the off and on states. We propose a revised structural model of the tetrameric FtsLB (named the “Y-model”) in which the periplasmic domain splits into a pair of coiled-coil branches. In this configuration, the hydrophilic terminal moieties of the polar amino acids remain more favorably exposed to water than in the original four-helix bundle model (“I-model”). We propose that a shift in this architecture, dependent on its marginal stability, is involved in activating the FtsLB complex and triggering septal cell wall reconstruction.
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