title: Switch or funnel: how RND-type transport systems control periplasmic metal homeostasis.
abstract: Bacteria have evolved several transport mechanisms to maintain metal homeostasis and to detoxify the cell. One mechanism involves an RND (resistance-nodulation-cell division protein family)-driven tripartite protein complex to extrude a variety of toxic substrates to the extracellular milieu. These efflux systems are comprised of a central RND proton-substrate antiporter, a membrane fusion protein, and an outer membrane factor. The mechanism of substrate binding and subsequent efflux has yet to be elucidated. However, the resolution of recent protein crystal structures and genetic analyses of the components of the heavy-metal efflux family of RND proteins have allowed the developments of proposals for a substrate transport pathway. Here two models of substrate extrusion through RND protein complexes of the heavy-metal efflux protein family are described. The funnel model involves the shuttling of periplasmic substrate from the membrane fusion protein to the RND transporter and further on through the outer membrane factor to the extracellular space. Conversely, the switch model requires substrate binding to the membrane fusion protein, inducing a conformational change and creating an open-access state of the tripartite protein complex. The extrusion of periplasmic substrate bypasses the membrane fusion protein, enters the RND-transporter directly via its substrate-binding site, and is ultimately eliminated through the outer membrane channel. Evidence for and against the two models is described, and we propose that current data favor the switch model.
authors.affiliation: Department of Soil, Water, and Environmental Science, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Eun-Hae
authors.initials: EH
authors.lastname: Kim
authors.forename: Dietrich H
authors.initials: DH
authors.lastname: Nies
authors.forename: Megan M
authors.initials: MM
authors.lastname: McEvoy
authors.forename: Christopher
authors.initials: C
authors.lastname: Rensing
mesh_terms: D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D019897:Periplasm / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D008670:Metals