Coiled-coil modules for designed molecular and cellular logic circuits

Roman Jerala

Roman Jerala

Coiled-coil (CC) dimers are ubiquitous building modules in natural proteins. Rules that define interactions in CC dimers are relatively understood, which allows us to design new CC dimers with selected stability and selectivity. Although CC dimers occur frequently in natural proteins, designed CC dimers can be used for cell regulation and construction of new building modules to regulate cellular processes. Designed CC dimer-forming peptides can be fused to other proteins, enabling regulation of biological processes, including localization within mammalian cells, augmented transcriptional response based on chemical regulators (CCCtag) and faster kinetics based on combination of split proteases with coiled-coil modules (SPOC logic)(1,2). Those building blocks have also been used to construct genetically encoded orthogonal secretion
systems for fast secretion of proteins based on the ER-retained proteins (3). Furthermore, formation of CC dimers has been used to introduce allosteric regulation of function of diverse proteins, comprising different folds and biological role, from enzymes, DNA binding proteins, signaling mediators, antibodies, which can be generate switches and logic functions with response time within minutes in mammalian cells (4) and introduce new type of control for research or biotechnological or therapeutic applications.

1. Fink et al. Chem Biol. (2018) 15 (2), 115-122.
2. Lebar et al. Nat. Chem.Biol. (2020) 16 (5), 513-519.
3. Praznik et al., Nat.Commun. (2022) 1323.
4. Plaper et al. bioRxiv (2022)

 

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