Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Department of Physics, University of California at Merced, Merced, CA, 95343, USA.
Nat Commun. 2020 Mar 16;11(1):1408. doi: 10.1038/s41467-020-14752-9.
In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its organization in vivo. Here, we perform molecular dynamics simulations for Caulobacter crescentus MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that successfully predicts MreB filament properties in vivo. Our analyses indicate that MreB double protofilaments can exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting correlates with the length and orientation of MreB filaments observed in vitro and in vivo. Our molecular dynamics simulations also suggest that membrane binding of MreB double protofilaments induces a stable membrane curvature of similar magnitude to that observed in vivo. Thus, our multiscale modeling correlates cytoskeletal filament size with conformational changes inferred from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular organization and function.
在许多杆状细菌中，肌动蛋白同源物 MreB 指导细胞壁的插入并维持细胞形状，但目前尚不清楚 MreB 的结构变化如何影响其在体内的组织。在这里，我们对新月柄杆菌的 MreB 进行分子动力学模拟，以提取机械参数并将其输入到粗粒生物物理聚合物模型中，该模型成功预测了体内 MreB 丝的性质。我们的分析表明，MreB 双原丝可以表现出依赖于结合核苷酸和膜结合的左手扭曲；扭曲的程度与体外和体内观察到的 MreB 丝的长度和方向相关。我们的分子动力学模拟还表明，MreB 双原丝的膜结合诱导与体内观察到的相似大小的稳定膜曲率。因此，我们的多尺度建模将细胞骨架丝的大小与从分子动力学模拟推断出的构象变化相关联，为连接蛋白质丝结构和力学与细胞组织和功能提供了范例。
