title: Electrochemical activation of engineered protein switches.
abstract: Engineered protein switches have a large dynamic range, high specificity for the activating ligand, and a modular architecture, and have been explored for a wide range of applications including biosensors and therapeutics. The ability to externally control switch function is important in extending applications for protein switches. We recently demonstrated that the on/off state could be controlled by the redox state of disulfide bonds introduced into the switches at select locations. Here, we demonstrate that an electrochemical signal can be used as an exogenous input to control switch function via reduction of the engineered disulfide bonds. This study suggests that disulfide-containing protein switch is a potentially useful platform for bioelectronic sensors with remote control of the sensing ability.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland, 21218.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland, 21218. oster@jhu.edu.
authors.forename: Maya
authors.initials: M
authors.lastname: Zayats
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland, 21218.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Searson
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland, 21218.
authors.forename: Marc
authors.initials: M
authors.lastname: Ostermeier
mesh_terms: D004220:Disulfides; D010084:Oxidation-Reduction; D011487:Protein Conformation; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004220:Disulfides; D011506:Proteins
keywords: allostery; disulfide bond; electrochemical reduction; protein engineering; protein switch