ArticleProceedings of the National Academy of Sciences of the United States of America2023
Differential dynamics and direct interaction of bound ligands with lipids in multidrug transporter ABCG2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- ABCG2 transporter: Structural and functional associations with gout (Review).International journal of molecular medicine · 2026Review
- Review
- The fourth-generation EGFR tyrosine kinase inhibitor BLU-945 resensitizes ABCG2-overexpressing multidrug-resistant non-small cell lung cancer cells to cytotoxic anticancer drugs.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025Article
- Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation.Nature communications · 2025Article
- Resurrection of the Helical Hairpin Hypothesis for Understanding Coronavirus Fusion.The Journal of membrane biology · 2025Review
- Synergistic activation of bat SARS-like coronaviruses spike protein by elastase and TMPRSS2.Scientific reports · 2025Article
- ABCG2 Transporter: From Structure to Function-Current Insights and Open Questions.International journal of molecular sciences · 2025Review
- Revisiting the Role of the Leucine Plug/Valve in the Human ABCG2 Multidrug Transporter.International journal of molecular sciences · 2025Article
- Dissecting Large-Scale Structural Transitions in Membrane Transporters Using Advanced Simulation Technologies.The journal of physical chemistry. B · 2025Review
- Article
- Article
- Membrane-dependent dynamics and dual translocation mechanisms of ABCB4: Insights from molecular dynamics simulations.Computational and structural biotechnology journal · 2025Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Modulation of ABCG2 Transporter Activity by Ko143 Derivatives.ACS chemical biology · 2024Article
- Topological Learning Approach to Characterizing Biological Membranes.Journal of chemical information and modeling · 2024Article
- Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance.Biomolecules · 2024Review
- Epidermal Growth Factor Receptor Inhibitor Mobocertinib Resensitizes Multidrug-Resistant Cancer Cells by Attenuating the Human ATP-Binding Cassette Subfamily B Member 1 and Subfamily G Member 2.ACS pharmacology & translational science · 2024Article
- Membrane-assisted tariquidar access and binding mechanisms of human ATP-binding cassette transporter P-glycoprotein.Frontiers in molecular biosciences · 2024Article
- Topological Learning Approach to Characterizing Biological Membranes.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
ABCG2 is an ATP-binding cassette (ABC) transporter that extrudes a wide range of xenobiotics and drugs from the cell and contributes to multidrug resistance in cancer cells. Following our recent structural characterization of topotecan-bound ABCG2, here, we present cryo-EM structures of ABCG2 under turnover conditions in complex with a special modulator and slow substrate, tariquidar, in nanodiscs. The structures reveal that similar to topotecan, tariquidar induces two distinct ABCG2 conformations under turnover conditions (turnover-1 and turnover-2). μs-scale molecular dynamics simulations of drug-bound and apo ABCG2 in native-like lipid bilayers, in both topotecan- and tariquidar-bound states, characterize the ligand size as a major determinant of its binding stability. The simulations highlight direct lipid-drug interactions for the smaller topotecan, which exhibits a highly dynamic binding mode. In contrast, the larger tariquidar occupies most of the available volume in the binding pocket, thus leaving little space for lipids to enter the cavity and interact with it. Similarly, when simulating ABCG2 in the apo inward-open state, we also observe spontaneous penetration of phospholipids into the binding cavity. The captured phospholipid diffusion pathway into ABCG2 offers a putative general path to recruit any hydrophobic/amphiphilic substrates directly from the membrane. Our simulations also reveal that ABCG2 rejects cholesterol as a substrate, which is omnipresent in plasma membranes that contain ABCG2. At the same time, cholesterol is found to prohibit the penetration of phospholipids into ABCG2. These molecular findings have direct functional ramifications on ABCG2's function as a transporter.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.