对于OmpR和NarL响应调节器子家族的残留同进化和突变格局
Mayu Shibata1, Xingcheng Lin2, José N Onuchic3
1Graduate School of Humanities and Sciences, Ochanomizu University, Bunkyo, Tokyo, Japan; Center for Theoretical Biological Physics, Rice University, Houston Texas.
Biophysical journal
|January 31, 2024
概括
了解DNA结合反应调节器 (DBRRs) 中的残留相互作用是改善细菌生物传感器设计的关键. 这项研究揭示了对DBRR相互作用的进化见解,有助于创建更具功能性的工程蛋白质.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物信息学是一种生物信息学.
背景情况:
- 细菌中的双组件信号传导系统依赖于与伴侣激酶相互作用的DNA结合反应调节器 (DBRRs).
- DBRRs通常具有N端信号传感和C端DNA结合域,通常被认为是功能独立的.
- 重组这些域为新型生物传感器提供了一条途径,但由于对域互动的不完全理解,成功率受到限制.
研究的目的:
- 调查OmpR和NarL DBRR子家族中链接域和域间残留相互作用的进化特征.
- 确定以前未知的域间相互作用及其在DBRR无活化中的潜在作用.
- 评估共进化分析对预测工程DBRR变体的功能有用性的评估.
主要方法:
- 在大型细菌序列数据集中对残留物共进化的分析.
- 检查左边域和域间区域的进化特征.
- 应用共同进化的景观模型来预测蛋白质功能.
主要成果:
- 发现了进化选择的链接器-域和域间残留相互作用,包括新的相互作用.
- 确定了潜在的域间接触,稳定了不活跃的DBRR构造,抑制了DNA结合.
- 证明了同进化模型的高负预测值,用于过非功能工程 DBRRs.
结论:
- 对DBRR域间相互作用和非激活机制的洞察力提高了对其功能机制的理解.
- 这些知识有助于高效设计基于DBRR的功能生物传感器.
- 同进化的景观模型提供了一种可行的方法,可以根据序列数据预测和过工程DBRR蛋白的功能.
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