Understanding the mechanism of a drug efflux pump


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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Zolnerciks JK, Akkaya BG, Snippe M, Chiba P, Seelig A, Linton KJ. The Q-loops of the Human Multidrug Resistance Transporter ABCB1 are Necessary to Couple Drug Binding to the ATP Catalytic Cycle. FASEB J. (2014) 10: 4335-46.


Zolnerciks JK, Wooding C and Linton KJ. Evidence for a Sav1866-like architecture for the human multidrug transporter P-glycoprotein. FASEB J. (2007) 21, 3937-48.


Di Bartolo N.D., Hvorup R.N., Locher K.P. & Booth P.J. In Vitro Folding and Assembly of the Escherichia coli ATP-binding Cassette Transporter, BtuCD. J. Biol. Chem. (2011) 286, 18807-18815.


Findlay, H.E., Rutherford, N.G., Henderson, P.J.F. & Booth, P.J. The unfolding free energy of a two-domain transmembrane sugar transport protein. Proc. Natl. Acad. Sci. USA. (2010) 107, 18451-18456.

Biological Areas:

Structural Biology
Chemical Biology


Molecules, cells and industrial biotechnology