Structural and mechanistic diversity of ABC transporters
Douglas Rees is interested in the structure and function of metalloproteins and membrane proteins, particularly those involved in cellular energy metabolism. His group’s metalloprotein work defined the unusual structures of the nitrogenase FeMo-cofactor and the more widespread Mo-cofactor that participate in basic reactions of the biological nitrogen and sulfur cycles, while the membrane protein studies have addressed energy-transduction processes associated with photosynthesis, mechanosensation and transport. Dr. Rees’s current work on membrane proteins centers on bacterial mechanosensitive channels and ATP-dependent bacterial transporters mediating the translocation of transition metals and nutrients.
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 the high affinity methionine MetNI importer and of a bacterial homologue of the mitochondrial Atm1 exporter 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 observed for MetNI, additional domains may be present that can regulate transport activity. Building on this qualitative molecular framework for deciphering the transport cycle, 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.
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