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Project

3-dimensional structure and function of a cyclic nucleotide-gated ion channel

Ligand-gated ion channels (LGICs) are integral membrane proteins that act as electrochemical switches in the central nervous system and are essential to its normal function. Furthermore, LGICs are the target for a wide variety of clinically available drugs and mutations in LGIC genes are responsible for a range of inherited diseases. Our specific goal is to gain mechanistic insight into ion channel function and understand the structural determinants of ligand recognition, the conformational changes underlying channel gating and the principles of ion selection and permeation in LGICs. Our methodological approach is based on electrophysiological techniques to understand function, in combination with structural methods such as X-ray crystallography and cryo-electron microscopy to understand structure. At present we are pursuing structures of the cyclic nucleotide-gated ion channel SthK.The proposed experiments will reveal structural principles for understanding the biological function and mechanism of cyclic nucleotide-modulated ion channels, laying the foundation for the potential development of new therapeutic agents.
Date:1 Oct 2017 →  30 Sep 2021
Keywords:ion channel
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing