Coiled-coil (CC) dimers are versatile, customizable building modules for the design of diverse protein architectures unknown in nature. Incorporation of dynamic self-assembly, regulated by a selected chemical signal, represents an important challenge in the construction of functional polypeptide nanostructures. Here, we engineered metal binding sites to render an orthogonal set of CC heterodimers Zn(II)-responsive as a generally applicable principle. The designed peptides assemble into CC heterodimers only in the presence of Zn(II) ions, reversibly dissociate by metal ion sequestration, and additionally act as pH switches, with low pH triggering disassembly. The developed Zn(II)-responsive CC set is used to construct programmable folding of CC-based nanostructures, from protein triangles to a two-chain bipyramidal protein cage that closes and opens depending on the metal ion. This demonstrates that dynamic self-assembly can be designed into CC-based protein cages by incorporation of metal ion–responsive CC building modules that act as conformational switches and that could also be used in other contexts.

中文翻译：

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设计的模块化蛋白质笼的金属离子调节组装

盘绕线圈 (CC) 二聚体是通用的、可定制的构建模块，用于设计自然界未知的多种蛋白质结构。由选定的化学信号调节的动态自组装的结合代表了构建功能性多肽纳米结构的重要挑战。在这里，我们设计了金属结合位点，以将一组正交的 CC 异二聚体 Zn(II) 响应作为普遍适用的原则。设计的肽仅在存在 Zn(II) 离子的情况下组装成 CC 异二聚体，通过金属离子螯合可逆地解离，另外还充当 pH 开关，低 pH 触发分解。开发的 Zn(II) 响应 CC 组用于构建基于 CC 的纳米结构的可编程折叠，从蛋白质三角形到根据金属离子关闭和打开的双链双锥体蛋白质笼。这表明动态自组装可以设计成基于 CC 的蛋白质笼，方法是结合作为构象开关的金属离子响应 CC 构建模块，也可以在其他情况下使用。