ATP binding cassette (ABC) transporters are primary active pumps that hydrolyse ATP to efflux solutes from cells. Some, like the human multidrug resistance P-glycoprotein (ABCB1), are polyspecific and pump many compounds, including toxins and therapeutic drugs, from cells. How these transporters work is poorly understood. We will investigate the mechanism by introducing mutations into key motifs within the protein to characterise the effect on protein function using a combination of cell biological and in vitro techniques. This will address the nature of their polyspecificty, and also how the drug binding and debinding events are coupled to the ATP catalytic cycle.
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