Skip to main content

A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells

16Citations
Citations of this article
146Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Protein interactions guide most cellular processes. Orthogonal hetero-specific protein–protein interaction domains may facilitate better control of engineered biological systems. Here, we report a tunable de novo designed set of orthogonal coiled-coil (CC) peptide heterodimers (called the NICP set) and its application for the regulation of diverse cellular processes, from cellular localization to transcriptional regulation. We demonstrate the application of CC pairs for multiplex localization in single cells and exploit the interaction strength and variable stoichiometry of CC peptides for tuning of gene transcription strength. A concatenated CC peptide tag (CCC-tag) was used to construct highly potent CRISPR–dCas9-based transcriptional activators and to amplify the response of light and small molecule-inducible transcription in cell culture as well as in vivo. The NICP set and its implementations represent a valuable toolbox of minimally disruptive modules for the recruitment of versatile functional domains and regulation of cellular processes for synthetic biology.

Cite

CITATION STYLE

APA

Lebar, T., Lainšček, D., Merljak, E., Aupič, J., & Jerala, R. (2020). A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells. Nature Chemical Biology, 16(5), 513–519. https://doi.org/10.1038/s41589-019-0443-y

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free