Marklew C J, Booth A, Beales P A, Ciani B
Department of Chemistry and Centre for Membrane Interactions and Dynamics, University of Sheffield, Sheffield, UK.
School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.
Interface Focus. 2018 Oct 6;8(5):20180035. doi: 10.1098/rsfs.2018.0035. Epub 2018 Aug 17.
The complexity of eukaryotic cells is underscored by the compartmentalization of chemical signals by phospholipid membranes. A grand challenge of synthetic biology is building life from the 'bottom-up', for the purpose of generating systems simple enough to precisely interrogate biological pathways or for adapting biology to perform entirely novel functions. Achieving compartmentalization of chemistries in an addressable manner is a task exquisitely refined by nature and embodied in a unique membrane remodelling machinery that pushes membranes away from the cytosol, the ESCRT-III (endosomal sorting complex required for transport-III) complex. Here, we show efforts to engineer a single ESCRT-III protein merging functional features from its different components. The activity of such a designed ESCRT-III is shown by its ability to drive the formation of compartments encapsulating fluorescent cargo. It appears that the modular nature of ESCRT-III allows its functional repurposing into a minimal machinery that performs sophisticated membrane remodelling, therefore enabling its use to create eukaryotic-like multi-compartment architectures.
磷脂膜对化学信号的区室化突出了真核细胞的复杂性。合成生物学的一个重大挑战是“自下而上”构建生命,目的是生成足够简单的系统以精确探究生物途径,或使生物学适应执行全新的功能。以可寻址的方式实现化学物质的区室化是一项大自然精心完善的任务,并体现在一种独特的膜重塑机制中,该机制将膜从细胞质中推开,即运输所需内体分选复合物III(ESCRT-III)复合物。在这里,我们展示了改造单一ESCRT-III蛋白以融合其不同组件功能特征的努力。这种设计的ESCRT-III的活性通过其驱动包裹荧光货物的区室形成的能力得以体现。ESCRT-III的模块化性质似乎使其能够功能重新利用,成为执行复杂膜重塑的最小机制,因此能够用于创建类似真核细胞的多区室结构。