ABC exporter function within their lipid microenvironment (P27)

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ATP binding cassette (ABC) exporters are essential contributors to the emergence of multidrugresistance. They form a microcompartment with their surrounding lipids, and the compositionof this microenvironment directly affects their conformational spectrum, as well as theirtransport efficiency. The molecular causes of this remain unknown, as thorough comparativestudies, recapitulating the protein-lipid composition of the microcompartment are challenging.Using cryo-EM, we have recently described the conformational spectrum of the heterodimericABC transporter TmrAB in a lipid environment and were able to address multiple long-standingcontroversies. With this project, we will systematically characterize the impact ofmicrocompartment composition on the dynamics of a homodimeric ABC exporter. We willinvestigate how the transporter initiates binding to a substrate and structurally determine itsconformations in different hydrophobic environments. We expect that our research will havefar-reaching implications in ABC transporter biology and of conformational dynamics ofmembrane proteins in general. This project will add a high-resolution angle to the descriptionof microcompartments and will contribute the method of cryo-EM to the research center.