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ABSTRACT Much structural information has been amassed on ATP-binding cassette (ABC) transporters, including hundreds of structures of isolated domains and an increasing array of full-length
transporters. The structures capture different steps in the transport cycle and have aided in the design and interpretation of computational simulations and biophysics experiments. These
data provide a maturing, although still incomplete, elucidation of the protein dynamics and mechanisms of substrate selection and transit through the transporters. We present an updated view
of the classical alternating-access mechanism as it applies to eukaryotic ABC transporters, focusing on type I exporters. Our model helps frame the progress in, and remaining questions
about, transporter energetics, how substrates are selected and how ATP is consumed to perform work at the molecular scale. Many human ABC transporters are associated with disease; we
highlight progress in understanding their pharmacology through the lens of structural biology and describe how this knowledge suggests approaches to pharmacologically targeting these
transporters. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access
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BEING VIEWED BY OTHERS ASYMMETRIC DRUG BINDING IN AN ATP-LOADED INWARD-FACING STATE OF AN ABC TRANSPORTER Article 20 December 2021 THE NET ELECTROSTATIC POTENTIAL AND HYDRATION OF ABCG2
AFFECT SUBSTRATE TRANSPORT Article Open access 18 August 2023 ON THE INTERPLAY BETWEEN LIPIDS AND ASYMMETRIC DYNAMICS OF AN NBS DEGENERATE ABC TRANSPORTER Article Open access 03 February
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PubMed Central Google Scholar Download references ACKNOWLEDGEMENTS We thank A. Murray and members of the laboratories of R.G. and A. Murray for insightful discussions. This work was funded
in part by NIH grant R01GM120996 (to R.G.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA Sriram Srikant
& Rachelle Gaudet Authors * Sriram Srikant View author publications You can also search for this author inPubMed Google Scholar * Rachelle Gaudet View author publications You can also
search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Rachelle Gaudet. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests.
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SUPPLEMENTARY INFORMATION Supplementary Table 1 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Srikant, S., Gaudet, R. Mechanics and pharmacology of
substrate selection and transport by eukaryotic ABC exporters. _Nat Struct Mol Biol_ 26, 792–801 (2019). https://doi.org/10.1038/s41594-019-0280-4 Download citation * Received: 29 December
2018 * Accepted: 17 July 2019 * Published: 26 August 2019 * Issue Date: September 2019 * DOI: https://doi.org/10.1038/s41594-019-0280-4 SHARE THIS ARTICLE Anyone you share the following link
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