ABCG2: does resolving its structure elucidate the mechanism?

Biochem Soc Trans. 2018 Dec 17;46(6):1485-1494. doi: 10.1042/BST20180145. Epub 2018 Nov 21.

Abstract

ABCG2 is one of a few human membrane transporters which display the amazing ability to transport multiple different chemicals out of cells. These multidrug pumps, which have orthologues in all organisms, are important in humans in the context of drug pharmacokinetics, especially with respect to resistance to chemotherapy. In 2016, we presented a mini-review on ABCG2 which identified many areas of exciting research progress as well as many areas of frustrating ignorance. Just 2 years on the field has advanced, particularly with respect to structural biology as the cryo-electron microscopy revolution has brought us new insights into the structure and mechanism of ABCG2. In this update, we evaluate the degree to which new data have enhanced our understanding of the structure and mechanism of ABCG2 and whether we are now in a position to translate some of these findings into inhibitor design and development.

Keywords: ABC transport proteins; electron microscopy; molecular modelling; multidrug resistance; pharmacokinetics; transmembrane proteins.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / chemistry*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / ultrastructure
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / metabolism
  • ATP-Binding Cassette Transporters / ultrastructure
  • Animals
  • Cryoelectron Microscopy
  • Drug Resistance, Multiple
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / ultrastructure

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Membrane Proteins