Structural and Mechanistic Principles of ABC Transporters

Annu Rev Biochem. 2020 Jun 20;89:605-636. doi: 10.1146/annurev-biochem-011520-105201.


ATP-binding cassette (ABC) transporters constitute one of the largest and most ancient protein superfamilies found in all living organisms. They function as molecular machines by coupling ATP binding, hydrolysis, and phosphate release to translocation of diverse substrates across membranes. The substrates range from vitamins, steroids, lipids, and ions to peptides, proteins, polysaccharides, and xenobiotics. ABC transporters undergo substantial conformational changes during substrate translocation. A comprehensive understanding of their inner workings thus requires linking these structural rearrangements to the different functional state transitions. Recent advances in single-particle cryogenic electron microscopy have not only delivered crucial information on the architecture of several medically relevant ABC transporters and their supramolecular assemblies, including the ATP-sensitive potassium channel and the peptide-loading complex, but also made it possible to explore the entire conformational space of these nanomachines under turnover conditions and thereby gain detailed mechanistic insights into their mode of action.

Keywords: ATPases; conformational dynamics; mechanochemical coupling; membrane proteins; molecular machines; multidrug resistance; transport cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / classification
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Bacteria / drug effects
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Binding Sites
  • Biological Transport
  • Biomechanical Phenomena
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Drug Resistance, Multiple / genetics*
  • Humans
  • Kinetics
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Substrate Specificity
  • Xenobiotics / metabolism
  • Xenobiotics / pharmacology


  • ATP-Binding Cassette Transporters
  • Xenobiotics
  • Adenosine Triphosphate