A Polymerization-Associated Structural Switch in FtsZ That Enables Treadmilling of Model Filaments.
A Polymerization-Associated Structural Switch in FtsZ That Enables Treadmilling of Model Filaments.
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DOI：
10.1128/mbio.00254-17
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发表时间：
2017-05-02
期刊：
影响因子：
6.4
通讯作者：
Löwe J
中科院分区：
文献类型：
--
作者：
Wagstaff JM;Tsim M;Oliva MA;García-Sanchez A;Kureisaite-Ciziene D;Andreu JM;Löwe J
许多生物体中的细菌细胞分裂涉及由微管蛋白样蛋白 FtsZ 协调的收缩细胞因子环。 FtsZ 在分裂部位靠近膜形成动态丝，最近显示这些丝在分裂环周围跑步，引导隔膜壁合成。在这里，我们利用金黄色葡萄球菌 FtsZ (SaFtsZ) 的 X 射线晶体学，揭示了 FtsZ 如何采用两种功能不同的构象：开放和闭合。开放形式存在于晶体中形成的 SaFtsZ 细丝中，并且也存在于通过电子冷冻显微镜推断的大肠杆菌 FtsZ 的可溶性细丝中。在两种非聚合 SaFtsZ 突变体的几种晶体形式中发现了闭合形式，并且对应于来自其他生物体的许多先前的 FtsZ 结构。我们认为 FtsZ 的构象转换与聚合相关，是由沿着细丝的纵向亚基间界面的形成驱动的。我们证明，这种开关可以解释单链细丝中如何发生跑步运动以及细丝组装为何是协作的。 FtsZ 蛋白是细菌细胞分裂过程中的关键分子。 FtsZ 形成细丝，组织细胞膜收缩，并重塑细胞壁，以分裂细胞。 FtsZ 通过核苷酸驱动的丝动力学发挥作用，但在分子水平上人们对此知之甚少。特别是，协作组装（对浓度的非线性依赖性）和跑步（长丝一端优先生长而另一端损失）的机制仍然难以捉摸。在这里，我们表明所有 FtsZ 蛋白很可能都具有两种不同的构象，单体 FtsZ 中的“闭合”形式和丝状中的“开放”形式。聚合时发生的构象转换解释了协同性，并与聚合依赖性核苷酸水解相一致，解释了 FtsZ 聚合物的高效跑步。
Bacterial cell division in many organisms involves a constricting cytokinetic ring that is orchestrated by the tubulin-like protein FtsZ. FtsZ forms dynamic filaments close to the membrane at the site of division that have recently been shown to treadmill around the division ring, guiding septal wall synthesis. Here, using X-ray crystallography of Staphylococcus aureus FtsZ (SaFtsZ), we reveal how an FtsZ can adopt two functionally distinct conformations, open and closed. The open form is found in SaFtsZ filaments formed in crystals and also in soluble filaments of Escherichia coli FtsZ as deduced by electron cryomicroscopy. The closed form is found within several crystal forms of two nonpolymerizing SaFtsZ mutants and corresponds to many previous FtsZ structures from other organisms. We argue that FtsZ’s conformational switch is polymerization-associated, driven by the formation of the longitudinal intersubunit interfaces along the filament. We show that such a switch provides explanations for both how treadmilling may occur within a single-stranded filament and why filament assembly is cooperative. The FtsZ protein is a key molecule during bacterial cell division. FtsZ forms filaments that organize cell membrane constriction, as well as remodeling of the cell wall, to divide cells. FtsZ functions through nucleotide-driven filament dynamics that are poorly understood at the molecular level. In particular, mechanisms for cooperative assembly (nonlinear dependency on concentration) and treadmilling (preferential growth at one filament end and loss at the other) have remained elusive. Here, we show that most likely all FtsZ proteins have two distinct conformations, a “closed” form in monomeric FtsZ and an “open” form in filaments. The conformational switch that occurs upon polymerization explains cooperativity and, in concert with polymerization-dependent nucleotide hydrolysis, efficient treadmilling of FtsZ polymers.