Physiologically, cyclic nucleotide-modulated ion channels play a role in signal transduction (e.g., in the olfactory and visual sensory systems) and pacemaking (e.g., in the heart and brain). They couple changes in the levels of intracellular signalling molecules with cellular electrical responses by adjusting the ion flux.
Knowledge of their structure will help guide pharmaceutical research.
The goal of our studies is to obtain the structure of the cyclic nucleotide-modulated potassium channel MloK1 in a close-to-native (lipid) environment under different conditions, (e.g., in the absence/presence of an interacting ligand) and, ultimately, at atomic resolution in order to fully understand its function.
For this, 2-D crystals of the lipid-embedded complex are produced and imaged at high resolution. Various software algorithms developed in-house help to reduce the effect of crystal imperfections, and sample movement and damage during imaging.