ATP-binding cassette (ABC) transmembrane proteins use the energy of bound ATP to drive the transport of hydrophobic substances, such as lipids and drugs, across all cell membranes.

For example, the human ABC transporter ABCA1 facilitates reverse cholesterol transport and catalyzes the assembly of high density lipoprotein. On the other hand, the transporters SLC47A1/2, which belong to the multidrug and toxic efflux (MATE) transporter family, remove various drugs from liver or kidney.

Dysfunction of either type of transporter leads to various diseases, such as Tangier disease. Despite its clinical relevance, the mechanism of transport of hydrophobic substances across biological membranes is poorly understood. We plan to overexpress and purify human ABC and MATE transporters and their bacterial homologues.

The X-ray structure of these transporters, once available, will help understand the molecular basis of the catalyzed processes and will support the design of novel inhibitors. Furthermore, we will test potential hydrophobic substrates with newly developed in vitro transport assays.