Structural and mechanistic diversity of ABC transporters

Abstract

ATP Binding Cassette (ABC) transporters constitute a ubiquitous superfamily of integral membrane proteins responsible for the ATP powered membrane translocation of a wide variety of substrates. The highly conserved ABC domains defining the superfamily provide the nucleotide powered engine that drives transport. In contrast, the transmembrane domains creating the translocation pathway are more variable, with three distinct folds currently recognized. Structural analyses of three bacterial importers, the BtuCD vitamin B12 importer and homologous HI1470/1, and the high affinity methionine MetNI importer, will be discussed within the mechanistic framework of the alternating access model. The interconversion of outward and inward facing conformations of the translocation pathway is coupled to the switching between open and closed interfaces of the ABC subunits that are associated with distinct nucleotide states. As with MetNI, additional domains may be present that can regulate transport activity. An important goal is to develop quantitative models that detail the kinetic and molecular mechanisms by which ABC transporters utilize the binding and hydrolysis of ATP to power substrate translocation.