SwitCCh: Metal-Site Design for Controlling the Assembly of a Coiled-Coil Homodimer.

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 ZnII ions or low pH. Addition of ZnII promoted formation of a parallel homodimer with an increase in thermal stability by more than 30 °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.