Lv Dashuai, Li Jingyuan, Ye Sheng
Life Sciences Institute, Zhejiang University, Hangzhou, China.
Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Institute of Quantitative Biology, Hangzhou, China.
Front Microbiol. 2021 Mar 30;12:639883. doi: 10.3389/fmicb.2021.639883. eCollection 2021.
Bacterial cytoskeletal protein FtsZ binds and hydrolyzes GTP, and assembles into dynamic filaments that are essential for cell division. Here, we used a multi-scale computational strategy that combined all-atom molecular dynamics (MD) simulations and coarse-grained models to reveal the conformational dynamics of assembled FtsZ. We found that the top end of a filament is highly dynamic and can undergo T-to-R transitions in both GTP- and GDP-bound states. We observed several subcategories of nucleation related dimer species, which leading to a feasible nucleation pathway. In addition, we observed that FtsZ filament exhibits noticeable amounts of twisting, indicating a substantial helicity of the FtsZ filament. These results agree with the previously models and experimental data. Anisotropy network model (ANM) analysis revealed a polymerization enhanced assembly cooperativity, and indicated that the cooperative motions in FtsZ are encoded in the structure. Taken together, our study provides a molecular-level understanding of the diversity of the structural states of FtsZ and the relationships among polymerization, hydrolysis, and cooperative assembly, which should shed new light on the molecular basis of FtsZ's cooperativity.
细菌细胞骨架蛋白FtsZ结合并水解GTP，并组装成动态细丝，这对细胞分裂至关重要。在此，我们使用了一种多尺度计算策略，该策略结合了全原子分子动力学（MD）模拟和粗粒度模型，以揭示组装后的FtsZ的构象动力学。我们发现细丝的顶端高度动态，并且在结合GTP和GDP的状态下都能经历从T态到R态的转变。我们观察到了几种与成核相关的二聚体种类的子类别，这导致了一条可行的成核途径。此外，我们观察到FtsZ细丝表现出明显的扭曲量，表明FtsZ细丝具有显著的螺旋度。这些结果与先前的模型和实验数据一致。各向异性网络模型（ANM）分析揭示了聚合增强的组装协同性，并表明FtsZ中的协同运动在结构中编码。综上所述，我们的研究提供了对FtsZ结构状态多样性以及聚合、水解和协同组装之间关系的分子水平理解，这应该为FtsZ协同性的分子基础提供新的线索。
