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Diversification of Protein Cage Structure Using Circularly Permuted Subunits

机译:使用循环排列的亚基的蛋白笼结构的多样化

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摘要

Self-assembling protein cages are useful as nanoscale molecular containers for diverse applications in biotechnology and medicine. To expand the utility of such systems, there is considerable interest in customizing the structures of natural cage-forming proteins and designing new ones. Here we report that a circularly permuted variant of lumazine synthase, a cage-forming enzyme from Aquifex aeolicus (AaLS) affords versatile building blocks for the construction of nanocompartments that can be easily produced, tailored, and diversified. The topologically altered protein, cpAaLS, self-assembles into spherical and tubular cage structures with morphologies that can be controlled by the length of the linker connecting the native termini. Moreover, cpAaLS proteins integrate into wild-type and other engineered AaLS assemblies by coproduction in Escherichia coli to form patchwork cages. This coassembly strategy enables encapsulation of guest proteins in the lumen, modification of the exterior through genetic fusion, and tuning of the size and electrostatics of the compartments. This addition to the family of AaLS cages broadens the scope of this system for further applications and highlights the utility of circular permutation as a potentially general strategy for tailoring the properties of cage-forming proteins.
机译:自组装蛋白笼可用作生物技术和医学中各种应用的纳米级分子容器。为了扩大这种系统的实用性,对定制天然形成笼子的蛋白质的结构和设计新的蛋白质有相当大的兴趣。在这里我们报告说,环丙氨酸合酶的圆形排列变体,一种来自Aquifex aeolicus(AaLS)的笼子形成酶,为构建纳米隔室提供了多种构建基块,可以轻松生产,定制和多样化。拓扑改变的蛋白质cpAaLS自组装成球形和管状笼状结构,其形态可通过连接天然末端的接头长度来控制。此外,cpAaLS蛋白通过在大肠杆菌中共同生产而整合到野生型和其他工程化的AaLS组件中,从而形成拼凑的笼子。这种共装配策略可将客体蛋白封装在管腔中,通过遗传融合修饰外部,并调节隔室的大小和静电。除了AaLS笼系列外,它还扩展了该系统的应用范围,并强调了圆形置换作为定制笼形蛋白特性的潜在通用策略的实用性。

著录项

  • 来源
    《Journal of the American Chemical Society》 |2018年第2期|558-561|共4页
  • 作者单位

    Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland;

    Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland;

    Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-18 03:07:16

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