SwitCCh: Metal-Site Design for Controlling the Assembly of a Coiled-Coil Homodimer
SwitCCh: Metal-Site Design for Controlling the Assembly of a Coiled-Coil Homodimer
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DOI：
10.1002/cbic.201800578
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发表时间：
2018-12-04
期刊：
影响因子：
3.2
通讯作者：
Jerala, Roman
中科院分区：
文献类型：
--
作者：
Aupic, Jana;Lapenta, Fabio;Jerala, Roman
蛋白质响应化学或物理信号的构象变化是生物系统中许多调节和运输机制的基本原理。设计蛋白质的构象状态可以精确和可逆地控制的能力将促进为特定应用定制的分子机器的发展。在这里，我们探索金属结合位点设计，以设计一种名为SwitCCh的基于肽的构象开关，该开关响应于Zn-II离子的添加或低pH值而组装成同二聚体卷曲螺旋。Zn-II的添加促进了平行同二聚体的形成，热稳定性增加了30摄氏度以上。该肽可以在卷曲螺旋和无规构象之间可逆循环。此外，SwitchCCh肽与先前开发的卷曲螺旋二聚体组正交，表明其可用于基于卷曲螺旋的纳米结构和材料的调节自组装。
Conformational change of proteins in response to chemical or physical signals is the underlying principle of many regulatory and transport mechanisms in biological systems. The ability to design proteins the conformational state of which can be precisely and reversibly controlled would facilitate the development of molecular machines tailored for specific applications. Here we explore metal-binding site design to engineer a peptide-based conformational switch called SwitCCh that assembles into a homodimeric coiled-coil in response to the addition of Zn-II ions or low pH. Addition of Zn-II promoted formation of a parallel homodimer with an increase in thermal stability by more than 30 degrees C. The peptide could be reversibly cycled between the coiled-coil and random conformation. Furthermore, the SwitCCh peptide was orthogonal to the previously developed coiled-coil dimer set, indicating it could be used for regulated self-assembly of coiled-coil based nanostructures and materials.