Switch or funnel: How RND-type transport systems control periplasmic metal homeostasis

Eun Hae Kim, Dietrich H. Nies, Megan M. McEvoy, Christopher Rensing

Research output: Contribution to journalShort surveypeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2381-2387
Number of pages7
JournalJournal of bacteriology
Issue number10
StatePublished - May 2011

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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