title: Downhill protein folding modules as scaffolds for broad-range ultrafast biosensors.
abstract: Conformational switches are macromolecules that toggle between two states (active/inactive or folded/unfolded) upon specific binding to a target molecule. These molecular devices provide an excellent scaffold for developing real-time biosensors. Here we take this concept one step beyond to build high-performance conformational rheostat sensors. The rationale is to develop sensors with expanded dynamic range and faster response time by coupling a given signal to the continuous (rather than binary) unfolding process of one-state downhill folding protein modules. As proof of concept we investigate the pH and ionic-strength sensing capabilities of the small α-helical protein BBL. Our results reveal that such a pH/ionic-strength sensor exhibits a linear response over 4 orders of magnitude in analyte concentration, compared to the 2 orders of magnitude for switches, and nearly concentration-independent microsecond response times.
authors.affiliation: Centro de Investigaciones Biológicas,  Consejo Superior de Investigaciones Científicas  (CSIC), Ramiro de Maeztu 9, Madrid 28040, Spain.
authors.forename: Michele
authors.initials: M
authors.lastname: Cerminara
authors.forename: Tanay M
authors.initials: TM
authors.lastname: Desai
authors.forename: Mourad
authors.initials: M
authors.lastname: Sadqi
authors.forename: Victor
authors.initials: V
authors.lastname: Muñoz
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009994:Osmolar Concentration; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013997:Time Factors
chemical_list: D011506:Proteins