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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein grafting of an HIV-1-inhibiting epitope.
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Protein grafting of an HIV-1-inhibiting epitope.

机译：抑制HIV-1抗原决定簇的蛋白质接枝。

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摘要

Protein grafting, the transfer of a binding epitope of one ligand onto the surface of another protein, is a potentially powerful technique for presenting peptides in preformed and active three-dimensional conformations. Its utility, however, has been limited by low biological activity of the designed ligands and low tolerance of the protein scaffolds to surface substitutions. Here, we graft the complete binding epitope (19 nonconsecutive amino acids with a solvent-accessible surface area of >2,000 A2) of an HIV-1 C-peptide, which is derived from the C-terminal region of HIV-1 gp41 and potently inhibits HIV-1 entry into cells, onto the surface of a GCN4 leucine zipper. The designed peptide, named C34coil, displays a potent antiviral activity approaching that of the native ligand. Moreover, whereas the linear C-peptide is unstructured and sensitive to degradation by proteases, C34coil is well structured, conformationally stable, and exhibits increased resistance to proteolytic degradation compared with the linear peptide. In addition to being a structured antiviral inhibitor, C34coil may also serve as the basis for the development of an alternative class of immunogens. This study demonstrates that "one-shot" protein grafting, without subsequent rounds of optimization, can be used to create ligands with structural conformations and improved biomedical properties.
机译：蛋白质接枝是将一个配体的结合表位转移到另一种蛋白质表面上的技术，它是一种潜在的强大技术，可以呈现预先形成的活性三维构象的肽。然而，其用途受到设计配体的低生物活性和蛋白质支架对表面取代的低耐受性的限制。在这里，我们嫁接了HIV-1 C肽的完整结合表位（19个非连续氨基酸，溶剂可及的表面积> 2,000 A2），该表位衍生自HIV-1 gp41的C端区域，抑制HIV-1进入细胞，并进入GCN4亮氨酸拉链的表面。设计的肽称为C34coil，显示出接近天然配体的有效抗病毒活性。此外，尽管线性C-肽是非结构化的并且对蛋白酶降解敏感，但是与线性肽相比，C34coil具有良好的结构，构象稳定，并且对蛋白水解降解显示出更高的抗性。除了是结构化的抗病毒抑制剂外，C34coil还可以作为开发另一类免疫原的基础。这项研究表明，“一口气”进行蛋白质嫁接，而无需随后的优化，可用于创建具有结构构象和改善的生物医学特性的配体。

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