Subunit interactions in ABC transporters: towards a functional architecture.
The ABC superfamily is a diverse group of integral membrane proteins involved in the ATP-dependent transport of solutes across biological membranes in both prokaryotes and eukaryotes. Although ABC transporters have been studied for over 30 years, very little is known about the mechanism by which the energy of ATP hydrolysis is used to transport substrate across the membrane. The recent report of the high resolution crystal structure of HisP, the nucleotide-binding subunit of the histidine permease complex of Salmonella typhimurium, represents a significant breakthrough toward the elucidation of the mechanism of solute translocation by ABC transporters. In this review, we use data from the crystallographic structures of HisP and other nucleotide-binding proteins, combined with sequence analysis of a subset of atypical ABC transporters, to argue a new model for the dimerisation of the nucleotide-binding domains that embraces the notion that the C motif from one subunit forms part of the ATP-binding site in the opposite subunit. We incorporate this dimerisation of the ATP-binding domains into our recently reported beta-barrel model for P-glycoprotein and present a general model for the cooperative interaction of the two nucleotide-binding domains and the translocation of mechanical energy to the transmembrane domains in ABC transporters.
Jones
P M
PM
Department of Cell and Molecular Biology, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, Sydney, N.S. W., Australia.
George
A M
AM
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001426:Bacterial Proteins; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
D018528:ATP-Binding Cassette Transporters; D026923:Amino Acid Transport Systems, Basic; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C043828:histidine permease, Bacteria; D000255:Adenosine Triphosphate