Design and Signaling Mechanism of Light-Regulated Histidine Kinases

• Published in: Journal of molecular biology Vol. 385; no. 5; pp. 1433 - 1444
• Main Authors: Möglich, Andreas, Ayers, Rebecca A., Moffat, Keith
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 06.02.2009
• Subjects: Amino Acid Sequence; Escherichia coli - enzymology; Histidine Kinase; Light; light-oxygen-voltage; Molecular Sequence Data; Per–Arnt–Sim; Phosphorylation; photosensor; protein design; Protein Kinases - chemistry; Protein Kinases - genetics; Protein Kinases - physiology; Protein Structure, Secondary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - physiology; reprogramming of signal specificity; Signal Transduction; photosensor; LOV; PAS; STAS; FMN; Per–Arnt–Sim; light-oxygen-voltage; reprogramming of signal specificity; protein design
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2008.12.017

Signal transduction proteins are organized into sensor (input) domains that perceive a signal and, in response, regulate the biological activity of effector (output) domains. We reprogrammed the input signal specificity of a normally oxygen-sensitive, light-inert histidine kinase by replacing its chemosensor domain by a light-oxygen-voltage photosensor domain. Illumination of the resultant fusion kinase YF1 reduced net kinase activity by ∼1000-fold in vitro. YF1 also controls gene expression in a light-dependent manner in vivo. Signals are transmitted from the light-oxygen-voltage sensor domain to the histidine kinase domain via a 40°–60° rotational movement within an α-helical coiled-coil linker; light is acting as a rotary switch. These signaling principles are broadly applicable to domains linked by α-helices and to chemo- and photosensors. Conserved sequence motifs guide the rational design of light-regulated variants of histidine kinases and other proteins.