Department of Chemistry, University of Illinois at Chicago, IL 60607, USA.
Department of Chemistry, University of Illinois at Chicago, IL 60607, USA; Department of Physics, University of Illinois at Chicago, IL 60607, USA.
J Mol Biol. 2022 Nov 15;434(21):167817. doi: 10.1016/j.jmb.2022.167817. Epub 2022 Sep 8.
Bacterial cell division begins with the formation of the Z-ring via polymerization of FtsZ and the localization of Z-ring beneath the inner membrane through membrane anchors. In Mycobacterium tuberculosis (Mtb), SepF is one such membrane anchor, but our understanding of the underlying mechanism is very limited. Here we used molecular dynamics simulations to characterize how SepF itself, a water-soluble protein, tethers to acidic membranes that mimic the Mtb inner membrane. In addition to an amphipathic helix (residues 1-12) at the N-terminus, membrane binding also occurs through two stretches of positively charged residues (Arg27-Arg37 and Arg95-Arg107) in the long linker preceding the FtsZ-binding core domain (residues 128-218). The additional interactions via the disordered linker stabilize the membrane tethering of SepF, and keep the core domain of SepF and hence the attached Z-ring close to the membrane. The resulting membrane proximity of the Z-ring in turn enables its interactions with and thus recruitment of two membrane proteins, FtsW and CrgA, at the late stage of cell division.
细菌细胞通过 FtsZ 的聚合和通过膜锚定在内膜下定位 Z 环开始分裂。在结核分枝杆菌（Mtb）中，SepF 就是这样一种膜锚，但其潜在机制我们知之甚少。在这里，我们使用分子动力学模拟来描述可溶性蛋白 SepF 本身如何与模拟 Mtb 内膜的酸性膜连接。除了 N 端的一个两亲性螺旋（残基 1-12）外，通过长连接子中的两个带正电荷的残基（Arg27-Arg37 和 Arg95-Arg107）与膜的结合也发生在 FtsZ 结合核心结构域（残基 128-218）之前。通过无序连接子的额外相互作用稳定了 SepF 的膜连接，从而使 SepF 的核心结构域和连接的 Z 环保持靠近膜。Z 环与膜的这种接近反过来又使其能够与两个膜蛋白 FtsW 和 CrgA 相互作用，并在细胞分裂的后期募集它们。
