Encoding extracellular modification of artificial cell membranes using engineered self-translocating proteins

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2024-10-30 DOI:10.1038/s41467-024-53783-4
Alexander Harjung, Alessandro Fracassi, Neal K. Devaraj
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Abstract

The development of artificial cells has led to fundamental insights into the functional processes of living cells while simultaneously paving the way for transformative applications in biotechnology and medicine. A common method of generating artificial cells is to encapsulate protein expression systems within lipid vesicles. However, to communicate with the external environment, protein translocation across lipid membranes must take place. In living cells, protein transport across membranes is achieved with the aid of complex translocase systems which are difficult to reconstitute into artificial cells. Thus, there is need for simple mechanisms by which proteins can be encoded and expressed inside synthetic compartments yet still be externally displayed. Here we present a genetically encodable membrane functionalization system based on mutants of pore-forming proteins. We modify the membrane translocating loop of α-hemolysin to translocate functional peptides up to 52 amino acids across lipid membranes. Full membrane translocation occurs in the absence of any translocase machinery and the translocated peptides are recognized by specific peptide-binding ligands on the opposing membrane side. Engineered hemolysins can be used for genetically programming artificial cells to display interacting peptide pairs, enabling their assembly into artificial tissue-like structures.

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利用工程自转移蛋白编码人工细胞膜的胞外修饰
人工细胞的开发使人们从根本上了解了活细胞的功能过程,同时也为生物技术和医学领域的变革性应用铺平了道路。生成人工细胞的一种常见方法是将蛋白质表达系统封装在脂质囊泡中。然而,要与外部环境进行交流,必须进行蛋白质跨脂膜转运。在活细胞中,蛋白质的跨膜转运是借助复杂的转运酶系统来实现的,而这些系统很难在人造细胞中重组。因此,我们需要一种简单的机制,既能在合成细胞内编码和表达蛋白质,又能在外部显示蛋白质。在这里,我们提出了一种基于孔形成蛋白突变体的基因编码膜功能化系统。我们对α-溶血素的膜转运环进行了改造,使其能在脂膜上转运多达 52 个氨基酸的功能肽。在没有任何转运酶机制的情况下,就能实现完全的膜转运,转运的多肽能被对膜侧的特异性多肽结合配体识别。工程溶血素可用于对人工细胞进行基因编程,使其显示相互作用的肽对,从而组装成人工组织样结构。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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