Subunit interactions in ABC transporters: towards a functional architecture

The ABC superfamily is a diverse group of integral membrane proteins involv ed in the ATP-dependent transport of solutes across biological membranes in both prokaryotes and eukaryotes. Although ABC transporters have been studi ed 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 membran e. 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 reward the elucidation o f the mechanism of solute translocation by ABC transporters. In this review , we use data from the crystallographic structures of HisP and other nucleo tide-binding proteins, combined with sequence analysis of a subset of atypi cal ABC transporters, to argue a new model for the dimerisation of the nucl eotide-binding domains that embraces the notion that the C motif from one s ubunit forms part of the ATP-binding site in the opposite subunit. We incor porate this dimerisation of the ATP-binding domains into our recently repor ted beta-barrel model for P-glycoprotein and present a general model for th e cooperative interaction of the two nucleotide-binding domains and the tra nslocation of mechanical energy to the transmembrane domains in ABC transpo rters. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.