Rational Design of Phosphorylation-Responsive Coiled Coil-Peptide Assemblies.

ABSTRACT: De novo peptides and proteins that switch state in response to chemical and physical cues would advance protein design and synthetic biology. Here we report two designed systems that disassemble and reassemble upon site-specific phosphorylation and dephosphorylation, respectively. As starting points, we use hyperthermostable de novo antiparallel and parallel coiled-coil heterotetramers, i.e., A₂B₂ systems, to afford control in downstream applications. The switches are incorporated by adding protein kinase A phosphorylation sites, R-R-X-S, with the phosphoacceptor serine residues placed to maximize disruption of the coiled-coil interfaces. The unphosphorylated peptides assemble as designed and unfold reversibly when heated. Addition of kinase to th

SUBMITTER: Thompson HF 

PROVIDER: S-EPMC10127268 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature