Complex state transitions of the bacterial cell division protein FtsZ.

IF 3.1 3区 生物学 Q3 CELL BIOLOGY Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI:10.1091/mbc.E23-11-0446
Benjamin D Knapp, Handuo Shi, Kerwyn Casey Huang
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Abstract

The key bacterial cell division protein FtsZ can adopt multiple conformations, and prevailing models suggest that transitions of FtsZ subunits from the closed to open state are necessary for filament formation and stability. Using all-atom molecular dynamics simulations, we analyzed state transitions of Staphylococcus aureus FtsZ as a monomer, dimer, and hexamer. We found that monomers can adopt intermediate states but preferentially adopt a closed state that is robust to forced reopening. Dimer subunits transitioned between open and closed states, and dimers with both subunits in the closed state remained highly stable, suggesting that open-state conformations are not necessary for filament formation. Mg2+ strongly stabilized the conformation of GTP-bound subunits and the dimer filament interface. Our hexamer simulations indicate that the plus end subunit preferentially closes and that other subunits can transition between states without affecting inter-subunit stability. We found that rather than being correlated with subunit opening, inter-subunit stability was strongly correlated with catalytic site interactions. By leveraging deep-learning models, we identified key intrasubunit interactions governing state transitions. Our findings suggest a greater range of possible monomer and filament states than previously considered and offer new insights into the nuanced interplay between subunit states and the critical role of nucleotide hydrolysis and Mg2+ in FtsZ filament dynamics.

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细菌细胞分裂蛋白 FtsZ 的复杂状态转换。
细菌细胞分裂的关键蛋白 FtsZ 可采用多种构象,流行的模型表明,从闭合态到开放态的转换是丝状体形成和稳定的必要条件。我们利用全原子分子动力学模拟分析了金黄色葡萄球菌 FtsZ 的单体、二聚体和六聚体的状态转换。我们发现,单体可以采用中间状态,但更倾向于采用一种闭合状态,这种状态对强制再开放具有稳健性。二聚体亚基在开放态和封闭态之间转换,而两个亚基都处于封闭态的二聚体保持高度稳定,这表明开放态构象并不是形成丝的必要条件。Mg2+ 强力稳定了与 GTP 结合的亚基构象和二聚体丝状界面。我们的六聚体模拟表明,加端亚基优先关闭,其他亚基可以在不同状态之间转换而不影响亚基间的稳定性。我们发现,亚基间稳定性与催化位点相互作用密切相关,而不是与亚基开放相关。通过利用深度学习模型,我们确定了控制状态转换的关键亚基内相互作用。我们的研究结果表明,可能的单体和丝状体状态的范围比以前考虑的要大,并为亚基状态之间微妙的相互作用以及核苷酸水解和 Mg2+ 在 FtsZ 丝状体动力学中的关键作用提供了新的见解。
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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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