Structure and mechanism of ABC transporter proteins.
ATP-binding cassette (ABC) transporters are ubiquitous membrane proteins that couple the transport of diverse substrates across cellular membranes to the hydrolysis of ATP. The crystal structures of four ABC transporters have recently been determined. They reveal similar arrangements of the conserved ATP-hydrolyzing nucleotide-binding domains, but unrelated architectures of the transmembrane domains, with the notable exception of a common 'coupling helix' that is essential for transmitting conformational changes. The structures suggest a mechanism that rationalizes ATP-driven transport: While binding of ATP appears to trigger an outward-facing conformation, dissociation of the hydrolysis products may promote an inward-facing conformation. This basic scheme can, in principle, explain nutrient import by ABC importers and drug extrusion by ABC exporters.
Hollenstein
Kaspar
K
Institute of Molecular Biology and Biophysics, ETH Zurich HPK D14.3, 8093 Zurich, Switzerland.
Dawson
Roger J P
RJ
Locher
Kaspar P
KP
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate