Light-Regulated Sensor Histidine Kinases - Structure, Dynamics & Optogenetics

Signal receptors comprise sensor modules which are responsive to chemical or physical stimuli and effector modules which possess biological activity. Interactions between sensor and effector are at the very basis of the signal-dependent modulation of biological activity, and a comprehensive biochemical, biophysical and structural characterization must involve intact sensor-effector entities. Our focus is on sensory photoreceptors which serve as light-regulated actuators in optogenetics. By employing the engineered light-oxygen-voltage photoreceptor YF1 as a paradigm, we capitalize on the dark-adapted structure of the full-length protein we recently determined. We seek to elucidate the conformational and dynamic transitions underpinning signal transduction and how they lead to regulation of effector activity. Structural information on the light-adapted state and reaction intermediates will be obtained by X-ray crystallography. In parallel, we will probe the dynamics of signal transduction by a combination of functional assays, electron paramagnetic resonance, infrared spectroscopy and hydrogen-deuterium exchange. Guided by molecular dynamic simulations, structural and dynamic data will be reconciled to reveal how photosensors and effector communicate. Structural and mechanistic principles evidenced in YF1 recur in diverse signalling proteins. An improved understanding of fundamental aspects of signal transduction will thus benefit the rational engineering of photoreceptors and their optogenetic deployment.

Principal Investigators
Möglich, Andreas Prof. Dr. (Details) (Junior Research Group 'Plasticity and Stability in Recurrent Systems of Spiking Neurons')

Duration of Project
Start date: 06/2013
End date: 05/2016

Last updated on 2020-26-11 at 14:20