Diversification of DNA-binding specificity via permissive and specificity-switching mutations in the ParB/Noc protein family
Diversification of DNA-binding specificity via permissive and specificity-switching mutations in the ParB/Noc protein family
复制标题
通过 ParB/Noc 蛋白家族的允许突变和特异性转换突变实现 DNA 结合特异性的多样化
DOI：
10.1101/724823
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Jalal A
中科院分区：
文献类型：
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作者：
Jalal A
蛋白质和DNA之间的特异性相互作用对许多生物过程至关重要。然而，目前还不清楚DNA结合特异性的多样化是如何产生的，导致特异性变化的突变途径也是未知的。使用一对进化上相关的DNA结合蛋白，每一个都有不同的DNA偏好（ParB [分配蛋白B]和Noc [类核闭塞因子]，它们都在细菌染色体维持中发挥作用），我们表明特异性是由蛋白质-DNA界面上的一组四个残基编码的。结合X射线晶体学和深层突变扫描的接口，我们建议，必须引入允许的突变之前的特异性转换突变重编程特异性和突变路径，以新的特异性不一定涉及双特异性中间体。总的来说，我们的研究结果提供了对ParB和Noc可能的进化历史的深入了解，并且在更广泛的背景下，可能有助于理解其他类别的DNA结合蛋白的进化。
Specific interactions between proteins and DNA are essential to many biological processes. Yet, it remains unclear how the diversification in DNA-binding specificity was brought about, and the mutational paths that led to changes in specificity are unknown. Using a pair of evolutionarily related DNA-binding proteins, each with a different DNA preference (ParB [Partitioning Protein B] and Noc [Nucleoid Occlusion Factor], which both play roles in bacterial chromosome maintenance), we show that specificity is encoded by a set of four residues at the protein-DNA interface. Combining X-ray crystallography and deep mutational scanning of the interface, we suggest that permissive mutations must be introduced before specificity-switching mutations to reprogram specificity and that mutational paths to new specificity do not necessarily involve dual-specificity intermediates. Overall, our results provide insight into the possible evolutionary history of ParB and Noc and, in a broader context, might be useful for understanding the evolution of other classes of DNA-binding proteins.