ArticleScientific reports2018
Mapping discontinuous epitopes for MRK-16, UIC2 and 4E3 antibodies to extracellular loops 1 and 4 of human P-glycoprotein.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Mutational analysis reveals the importance of residues of the access tunnel inhibitor site to human P-glycoprotein (ABCB1)-mediated transport.Protein science : a publication of the Protein Society · 2024Article
- Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance.Biomolecules · 2024Review
- Second-site suppressor mutations reveal connection between the drug-binding pocket and nucleotide-binding domain 1 of human P-glycoprotein (ABCB1).Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Article
- Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications.International journal of molecular sciences · 2023Article
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Residues from Homologous Transmembrane Helices 4 and 10 Are Critical for P-Glycoprotein (ABCB1)-Mediated Drug Transport.Cancers · 2023Article
- Cross-Linking Mass Spectrometry on P-Glycoprotein.International journal of molecular sciences · 2023Article
- The integrated comprehension of lncRNA HOXA-AS3 implication on human diseases.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Effects of Polyphenols on P-Glycoprotein (ABCB1) Activity.Pharmaceutics · 2021Article
- Use of photoimmunoconjugates to characterize ABCB1 in cancer cells.Nanophotonics (Berlin, Germany) · 2021Article
- Article
- Does the ATP-bound EQ mutant reflect the pre- or post-ATP hydrolysis state in the catalytic cycle of human P-glycoprotein (ABCB1)?FEBS letters · 2021Article
- Reversing the direction of drug transport mediated by the human multidrug transporter P-glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cryo-EM structures reveal distinct mechanisms of inhibition of the human multidrug transporter ABCB1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Linker Domains: Why ABC Transporters 'Live in Fragments no Longer'.Trends in biochemical sciences · 2020Review
- Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells.Biology · 2019Article
- Synthesis and Characterization of Bodipy-FL-Cyclosporine A as a Substrate for Multidrug Resistance-Linked P-Glycoprotein (ABCB1).Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Evidence for the critical role of transmembrane helices 1 and 7 in substrate transport by human P-glycoprotein (ABCB1).PloS one · 2018Article
- Photodynamic priming modulates cellular ATP levels to overcome P-glycoprotein-mediated drug efflux in chemoresistant triple-negative breast cancer.Photochemistry and photobiologyArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is associated with the development of multidrug resistance in cancer cells. Antibody-mediated blockade of human P-gp activity has been shown to overcome drug resistance by re-sensitizing resistant cancer cells to anticancer drugs. Despite the potential clinical application of this finding, the epitopes of the three human P-gp-specific monoclonal antibodies MRK-16, UIC2 and 4E3, which bind to the extracellular loops (ECLs) have not yet been mapped. By generating human-mouse P-gp chimeras, we mapped the epitopes of these antibodies to ECLs 1 and 4. We then identified key amino acids in these regions by replacing mouse residues with homologous human P-gp residues to recover binding of antibodies to the mouse P-gp. We found that changing a total of ten residues, five each in ECL1 and ECL4, was sufficient to recover binding of both MRK-16 and 4E3 antibodies, suggesting a common epitope. However, recovery of the conformation-sensitive UIC2 epitope required replacement of thirteen residues in ECL1 and the same five residues replaced in the ECL4 for MRK-16 and 4E3 binding. These results demonstrate that discontinuous epitopes for MRK-16, UIC2 and 4E3 are located in the same regions of ECL1 and 4 of the multidrug transporter.
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