Intermolecular domain swapping induces intein-mediated protein alternative splicing
Intermolecular domain swapping induces intein-mediated protein alternative splicing
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DOI：
10.1038/nchembio.1320
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发表时间：
2013-10-01
影响因子：
14.8
通讯作者：
Iwai, Hideo
中科院分区：
文献类型：
--
作者：
Aranko, A. Sesilja;Oeemig, Jesper S.;Iwai, Hideo
蛋白质序列通过重组和突变在DNA水平上多样化，并且可以通过选择性RNA剪接在RNA水平上进一步增加，涉及在许多生物过程中具有重要作用的内含子。内含子（内含肽）催化蛋白质剪接的蛋白质版本在20世纪90年代首次报道。蛋白质剪接的生物学作用仍然是难以捉摸的，因为内含肽既没有提供任何明确的好处，也没有在其宿主生物体中发挥重要作用。我们现在报告蛋白质选择性剪接，其中新的蛋白质序列可以通过蛋白质重组产生的分子间结构域交换的内含肽，如NMR光谱和晶体结构所阐明的。我们证明，内含肽介导的蛋白质选择性剪接可能是一种新的策略，以增加蛋白质的多样性（即功能），没有任何修改的遗传背景。我们还利用它作为翻译后蛋白质构象驱动的蛋白质功能开关（例如，作为高度特异性的蛋白质干扰）。
Protein sequences are diversified on the DNA level by recombination and mutation and can be further increased on the RNA level by alternative RNA splicing, involving introns that have important roles in many biological processes. The protein version of introns (inteins), which catalyze protein splicing, were first reported in the 1990s. The biological roles of protein splicing still remain elusive because inteins neither provide any clear benefits nor have an essential role in their host organisms. We now report protein alternative splicing, in which new protein sequences can be produced by protein recombination by intermolecular domain swapping of inteins, as elucidated by NMR spectroscopy and crystal structures. We demonstrate that intein-mediated protein alternative splicing could be a new strategy to increase protein diversity (that is, functions) without any modification in genetic backgrounds. We also exploited it as a post-translational protein conformation-driven switch of protein functions (for example, as highly specific protein interference).