Can I read Rational Design of Phosphorylation-Responsive Coiled Coil-Peptide Assemblies on EtoBox?

Rational Design of Phosphorylation-Responsive Coiled Coil-Peptide Assemblies by Harry F. Thompson; Joseph L. Beesley; Hannah D. Langlands; Caitlin L. Edgell; Nigel J. Savery; Derek N. Woolfson is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Rational Design of Phosphorylation-Responsive Coiled Coil-Peptide Assemblies about?

__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.__, A~2~B~2~ 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 the assembled states unfolds them with half-lives of ≤5 min. Phosphorylation is reversed by Lambda Protein Phosphatase resulting in tetramer reassembly. We envisage that the new __de novo__ designed coiled-coil components, the switches, and a mechanistic model for them will be useful in synthetic biology, biomaterials, and biotechnology applications.

Who reads Rational Design of Phosphorylation-Responsive Coiled Coil-Peptide Assemblies?

Author

Harry F. Thompson; Joseph L. Beesley; Hannah D. Langlands; Caitlin L. Edgell; Nigel J. Savery; Derek N. Woolfson

Publisher

American Chemical Society (ACS)

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)