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Updated: Dec 1, 2025

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
The first intracellular loop is essential for the catalytic cycle of the human ABCG2 multidrug resistance transporter
Narakorn Khunweeraphong1,2, Karl Kuchler1
1Max Perutz Labs Vienna, Center for Medical Biochemistry, Campus Vienna Biocenter, Medical University of Vienna, Austria.
Abstract:
The human multidrug transporter ABCG2 is required for physiological detoxification and mediates anticancer drug resistance. Here, we identify pivotal residues in the first intracellular loop (ICL1), constituting an intrinsic part of the transmission interface. The architecture includes a triple helical bundle formed by the hot spot helix of the nucleotide-binding domain, the elbow helix, and ICL1. We show here that the highly conserved ICL1 residues G462, Y463, and Y464 are essential for the proper cross talk of the closed nucleotide-binding domain dimer with the transmembrane domains. Hence, ICL1 acts as a molecular spring, triggering the conformational switch of ABCG2 before substrate extrusion. These data suggest that the ABCG2 transmission interface may offer therapeutic options for the treatment of drug-resistant malignancies.
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