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ABC transporters are divided into importers, found exclusively in bacteria, and exporters, present in all phyla of life. Transport processes mediated by more than forty human ABC exporters fulfill vital functions in our body as they translocate an extraordinarily wide range of cargoes such as lipids, peptides, ions and drugs across lipid bilayers. A number of severe hereditary diseases including cystic fibrosis and insulin secretion disorders such as neonatal diabetes and hyperinsulinism are directly linked to ABC transporter malfunction (CFTR and SUR1, respectively), underpinning their paramount importance in human health. The human ABC exporters P-glycoprotein, ABCG2 and MRP1 act as multidrug efflux pumps in tumors and hamper effective cancer treatment.
ABC exporters minimally consist of two transmembrane domains (TMDs) each containing six transmembrane helices which protrude far into the cytoplasm and two nucleotide binding domains (NBDs), which undergo large conformational changes in response to ATP binding and hydrolysis. Transport across the membrane requires substrate binding to the inward-facing cavity, NBD closure and transition to the outward-facing (OF) state and substrate release.


In our lab we investigate the whole transport cycle using EPR techniques. Double electron electron resonance (DEER) distance measurements and Overhauser dynamic nuclear polarization techniques are particularly useful for our aim. The paramagnetic spin probes are attached to the site of interest enabling us to accurately measure the distance between pairs of spin labels and/or study water accessibility and dynamics around the spin probe.



Collaboration partners:
Prof. Markus Seeger, University of Zurich, Switzerland
Prof. Erwin Schneider, Humboldt University Berlin, Germany
Prof. Robert Tampe´, Goethe University of Frankfurt, Germany