Domain coupling in the ABC transporter system BtuCD/BtuF: molecular dynamics simulation, normal mode analysis and protein-protein docking

Abstract

ATP binding cassette (ABC) transporters form a large class of proteins that use energy from ATP to power transport across biological membranes against the thermodynamic gradient. They consist of two water-soluble domains that are responsible for ATP hydrolysis and two transmembrane domains that form the transport pathway. In addition, they often interact with auxiliary domains or proteins that may regulate the transport process or deliver substrates. Recent crystal structures have revealed the molecular architecture of ABC transporters. We are using a combination of computational techniques to study the dynamics of ABC transporters, the possible mechanism by which the energy of ATP hydrolysis is used for transport, and the interactions between the different domains. We present an overview of our current understanding of the interactions between the domains of the vitamin Bu importer BtuCD, new simulation results from the BtuCD protein, and two models of the interactions of BtuCD with its substrate binding protein BtuF.