Abstract
Bacterial ATP-binding cassette (ABC) exporters embrace an enormous range of biological processes. They can mediate the efflux of a wide variety of substrates ranging from small inorganic ions, drugs, and antibiotics to large protein toxins and other macromolecules. They can also act as mediators and regulators in transmembrane signaling processes perhaps without mediating any direct transport reaction. This diversity in function of ABC exporters raises questions about their structure, how conformational changes are coupled to activity, and how we can use this information to inhibit, activate, or bypass physiological functions in drug-based strategies. When the first ABC transporters were discovered, now 40 years ago, it was noted by sequence comparisons that many of them shared a similar domain organization. But exactly how these domains cooperate in mediating transport activity was unknown. A wealth of biochemical studies and crystal structures of nucleotide-binding domains (NBDs), and subsequently of full-length ABC exporters, suggests that the general mechanism is based on metabolic energy-dependent alternating access of substrate-binding pocket(s) to either side of the phospholipid bilayer, but that there is diversity in the detailed molecular mechanisms that are being employed. This chapter provides an overview of the structural and mechanistic intricacies that have surfaced over the past years, and the challenges in further studies on these amazing transport proteins.
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Acknowledgments
Work in the author’s laboratory is funded by the Biotechnology and Biological Sciences Research Council, Medical Research Council, and Human Frontier Science Program. He is also grateful for support from the British Society for Antimicrobial Chemotherapy.
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van Veen, H.W. (2016). Bacterial ABC Multidrug Exporters: From Shared Proteins Motifs and Features to Diversity in Molecular Mechanisms. In: George, A. (eds) ABC Transporters - 40 Years on. Springer, Cham. https://doi.org/10.1007/978-3-319-23476-2_2
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DOI: https://doi.org/10.1007/978-3-319-23476-2_2
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Publisher Name: Springer, Cham
Print ISBN: 978-3-319-23475-5
Online ISBN: 978-3-319-23476-2
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