Lipid transport by ABC proteins [Elektronische Ressource] : studies on MDR1 P-Glycoprotein and breast cancer resistance protein / von Antje Pohl

Lipid Transport by ABC ProteinsStudies on MDR1 P-Glycoprotein and Breast Cancer Resistance ProteinDISSERTATIONzur Erlangung des akademischen Gradesdoctor rerum naturalium(Dr. rer. nat.)im Fach Biophysikeingereicht an derMathematisch-Naturwissenschaftlichen Fakultät Ider Humboldt Universität zu BerlinvonDiplom-Biophysikerin Antje Pohlgeboren am 16.04.73 in BerlinPräsident der Humboldt Universität zu BerlinProf. Dr. Jürgen MlynekDekan der Mathematisch-Naturwissenschaftlichen Fakultät IProf. Dr. Michael LinscheidGutachter:1. Prof. Dr. Andreas Herrmann2. Prof. Dr. Philippe Devaux3. Prof. Dr. Hermann-Georg HolzhütterTag der mündlichen Prüfung:19.07.02SummaryIn eukaryotic cells, the lipid species are frequently distributed asymmetrically between theplasma membrane leaflets. Phosphatidylserine (PS), in particular, often exhibits a distincttransverse asymmetry, being restricted almost exclusively to the inner leaflet.In the past years, several proteins were suggested to transport lipids between the leaflets ofa membrane, and to potentially influence transverse lipid asymmetry and related cellproperties.This thesis focuses on outward transport of fluorescent (C6-NBD-) lipid analogs andendogenous lipids by the Multidrug Resistance 1 P-Glycoprotein (MDR1 Pgp), a memberof the ATP binding cassette (ABC) transporter superfamily. Interestingly, MDR1 Pgp hasbeen suggested to exhibit an unusually broad substrate specificity.