Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas.
Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas.
Biophys J. 2021 Sep 7;120(17):3820-3830. doi: 10.1016/j.bpj.2021.05.032. Epub 2021 Jul 9.
Bacterial cells construct many structures, such as the flagellar hook and the type III secretion system (T3SS) injectisome, that aid in crucial physiological processes such as locomotion and pathogenesis. Both of these structures involve long extracellular channels, and the length of these channels must be highly regulated in order for these structures to perform their intended functions. There are two leading models for how length control is achieved in the flagellar hook and T3SS needle: the substrate switching model, in which the length is controlled by assembly of an inner rod, and the ruler model, in which a molecular ruler controls the length. Although there is qualitative experimental evidence to support both models, comparatively little has been done to quantitatively characterize these mechanisms or make detailed predictions that could be used to unambiguously test these mechanisms experimentally. In this work, we constructed a mathematical model of length control based on the ruler mechanism and found that the predictions of this model are consistent with experimental data-not just for the scaling of the average length with the ruler protein length, but also for the variance. Interestingly, we found that the ruler mechanism allows for the evolution of needles with large average lengths without the concomitant large increase in variance that occurs in the substrate switching mechanism. In addition to making further predictions that can be tested experimentally, these findings shed new light on the trade-offs that may have led to the evolution of different length control mechanisms in different bacterial species.
细菌细胞构建了许多结构,如鞭毛钩和 III 型分泌系统(T3SS)注射器,这些结构有助于运动和发病等关键生理过程。这两种结构都涉及到长的细胞外通道,并且为了使这些结构发挥其预期的功能,这些通道的长度必须高度调节。有两种主要的模型可以解释鞭毛钩和 T3SS 针的长度控制机制:底物切换模型,其中长度通过内杆的组装来控制;以及标尺模型,其中分子标尺控制长度。尽管有定性的实验证据支持这两种模型,但相对而言,定量表征这些机制或做出详细的预测的工作做得还很少,这些预测可以用于明确地通过实验来测试这些机制。在这项工作中,我们基于标尺机制构建了一个长度控制的数学模型,发现该模型的预测与实验数据一致——不仅与标尺蛋白长度的平均长度缩放一致,而且与方差一致。有趣的是,我们发现标尺机制允许具有较大平均长度的针的进化,而不会发生在底物切换机制中发生的方差的相应较大增加。除了做出可以通过实验测试的进一步预测外,这些发现还揭示了可能导致不同细菌物种中不同长度控制机制进化的权衡。