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Enzyme-Directed Functionalization of Designed, Two-Dimensional Protein Lattices

机译:设计,二维蛋白质格的酶官能化

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摘要

The design and construction of crystalline protein arrays to selectively assemble ordered nanoscale materials have potential applications in sensing, catalysis, and medicine. Whereas numerous designs have been implemented for the bottom-up construction of protein assemblies, the generation of artificial functional materials has been relatively unexplored. Enzyme-directed post-translational modifications are responsible for the functional diversity of the proteome and, thus, could be harnessed to selectively modify artificial protein assemblies. In this study, we describe the use of phosphopantetheinyl transferases (PPTases), a class of enzymes that covalently modify proteins using coenzyme A (CoA), to site-selectively tailor the surface of designed, two-dimensional (2D) protein crystals. We demonstrate that a short peptide (ybbR) or a molecular tag (CoA) can be covalently tethered to 2D arrays to enable enzymatic functionalization using Sfp PPTase. The site-specific modification of two different protein array platforms is facilitated by PPTases to afford both small molecule- and protein-functionalized surfaces with no loss of crystalline order. This work highlights the potential for chemoenzymatic modification of large protein surfaces toward the generation of sophisticated protein platforms reminiscent of the complex landscape of cell surfaces.
机译:用于选择性组装有序纳米材料的晶体蛋白质阵列的设计和构建在传感、催化和医学方面具有潜在的应用。尽管已经有许多设计用于蛋白质组装的自底向上构建,但人工功能材料的产生却相对未被探索。酶引导的翻译后修饰负责蛋白质组的功能多样性,因此,可以利用它来选择性地修饰人工蛋白质组装体。在这项研究中,我们描述了使用磷酸泛乙烯基转移酶(PPTases),一类使用辅酶a(CoA)共价修饰蛋白质的酶,来定位选择性地裁剪设计的二维(2D)蛋白质晶体的表面。我们证明了短肽(ybbR)或分子标记(CoA)可以共价连接到2D阵列,以使用Sfp-PPTase实现酶功能化。pptase促进了两种不同蛋白质阵列平台的位点特异性修饰,以提供小分子和蛋白质功能化表面,而不会失去结晶顺序。这项工作强调了化学酶法修饰大蛋白质表面以产生复杂蛋白质平台的潜力,使人想起细胞表面的复杂景观。

著录项

  • 来源
    《Biochemistry》 |2021年第13期|共13页
  • 作者单位

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

    Department of Chemistry and Biochemistry University of California;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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