The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Structure of the human multidrug transporter ABCG2
Open accessAbstract
ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. We visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. We observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, our results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters.
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Cites
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Self-citation
Cited by
Revisiting the role of ABC transporters in multidrug-resistant cancer
Robey, R. W., Pluchino, K. M., Hall, M. D., Fojo, A. T., Bates, S. E., & Gottesman, M. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0005-8 · Cited by 1,866
Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states
Manolaridis, I., Jackson, S. M., Taylor, N. M. I., Kowal, J., Stahlberg, H., & Locher, K. P. (2018) · Nature · doi:10.1038/s41586-018-0680-3 · Cited by 228
Self-citationABCG2 transports anticancer drugs via a closed-to-open switch
Orlando, B. J., & Liao, M. (2020) · Nature Communications · doi:10.1038/s41467-020-16155-2 · Cited by 198
Ins and outs of AlphaFold2 transmembrane protein structure predictions
Hegedűs, T., Geisler, M., Lukács, G. L., & Farkas, B. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04112-1 · Cited by 127
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Metadata
- Authors
- Taylor, N. M. I., Manolaridis, I., Jackson, S. M., Kowal, J., Stahlberg, H., & Locher, K. P.
- Venue
- Nature
- Published
- 2017-05-29
- Volume
- 546
- Issue
- 7659
- Pages
- 504-509
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2619656708
- Cited by
- 418
- References
- 9
- FWCI
- 19.82
- Type
- journal article
- Language
- en
- Open access
- green
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