Crystal structure analysis of a voltage-gated sodium channel

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Voltage-gated sodium channels (VGSC) are essential proteins enabling the transport of ions across cell membranes. They are found in all eukaryotic organisms and a range of bacteria. In humans as well as lower eukaryotes they are essential for normal functioning, and in higher organisms various isoforms are found in different tissues, ranging from heart to brain, with different functional roles in the healthy organism. Sodium channel mutations give rise to a number of disease states; as a result they are the targets of many pharmaceutical drugs, including ones for treatment of epilepsy and chronic pain. This proposal is to determine the crystal structure of a sodium channel, characterise its functional and binding properties, as a basis for understanding the structural basis of sodium channel functioning and its interactions with ligands, including drugs and insecticides.