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Mechanistic diversity in ATP-binding cassette (ABC) transporters

ABC transporters use ATP hydrolysis to translocate substrates across cell membranes. Kaspar Locher reviews the mechanistic diversity of ABC transporters, as has emerged from recent structural studies, and discusses future directions for investigation of ABC-transporter-catalyzed reactions.

Abstract

ABC transporters catalyze transport reactions, such as the high-affinity uptake of micronutrients into bacteria and the export of cytotoxic compounds from mammalian cells. Crystal structures of ABC domains and full transporters have provided a framework for formulating reaction mechanisms of ATP-driven substrate transport, but recent studies have suggested remarkable mechanistic diversity within this protein family. This review evaluates the differing mechanistic proposals and outlines future directions for the exploration of ABC-transporter-catalyzed reactions.

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Figure 1: Architecture of ABC transporters.
Figure 2: ABC-transporter structures.
Figure 3: Distinct mechanisms of type I and type II ABC importers.
Figure 4: Conformations in selected B-family ABC-exporter structures.
Figure 5: Distinct mechanisms of B-family ABC exporters.

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Acknowledgements

K.P.L. thanks A. Alam and C. Perez for critical reading of the manuscript. Research in the laboratory of K.P.L. has been supported by funds from ETH Zurich, the Swiss National Science Foundation (SNF), the Roche Research Fund, the Swiss Cancer League Oncosuisse, the National Centers for Excellence in Research (NCCR) Structural Biology and TransCure, and EMBO.

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Locher, K. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat Struct Mol Biol 23, 487–493 (2016). https://doi.org/10.1038/nsmb.3216

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