Distinct conformational spectrum of homologous multidrug ABC transporters

Structure. 2015 Mar 3;23(3):450-460. doi: 10.1016/j.str.2014.12.013. Epub 2015 Feb 5.


ATP-binding cassette (ABC) exporters are ubiquitously found in all kingdoms of life and their members play significant roles in mediating drug pharmacokinetics and multidrug resistance in the clinic. Significant questions and controversies remain regarding the relevance of their conformations observed in X-ray structures, their structural dynamics, and mechanism of transport. Here, we used single particle electron microscopy (EM) to delineate the entire conformational spectrum of two homologous ABC exporters (bacterial MsbA and mammalian P-glycoprotein) and the influence of nucleotide and substrate binding. Newly developed amphiphiles in complex with lipids that support high protein stability and activity enabled EM visualization of individual complexes in a membrane-mimicking environment. The data provide a comprehensive view of the conformational flexibility of these ABC exporters under various states and demonstrate not only similarities but striking differences between their mechanistic and energetic regulation of conformational changes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry*
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / ultrastructure*
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / ultrastructure*
  • Membrane Lipids / chemistry
  • Mice
  • Microscopy, Electron
  • Models, Molecular
  • Nucleotides / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Stability
  • Structural Homology, Protein


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Membrane Lipids
  • MsbA protein, Bacteria
  • Nucleotides