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Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter.

par Pak, John Edward;Ekendé, Elisabeth Ngonlong;Kifle, Efrem G;O'Connell, Joseph Daniel;De Angelis, Fabien ;Tessema, Meseret B;Derfoufi, Kheiro-Mouna ;Robles-Colmenares, Yaneth;Robbins, Rebecca A;Goormaghtigh, Erik ;Vandenbussche, Guy ;Stroud, Robert M
Référence Proceedings of the National Academy of Sciences of the United States of America
Publication Publié, 2013-10

Article révisé par les pairs

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Résumé :

Efflux pumps belonging to the ubiquitous resistance-nodulation-cell division (RND) superfamily transport substrates out of cells by coupling proton conduction across the membrane to a conformationally driven pumping cycle. The heavy metal-resistant bacteria Cupriavidus metallidurans CH34 relies notably on as many as 12 heavy metal efflux pumps of the RND superfamily. Here we show that C. metallidurans CH34 ZneA is a proton driven efflux pump specific for Zn(II), and that transport of substrates through the transmembrane domain may be electrogenic. We report two X-ray crystal structures of ZneA in intermediate transport conformations, at 3.0 and 3.7 Å resolution. The trimeric ZneA structures capture protomer conformations that differ in the spatial arrangement and Zn(II) occupancies at a proximal and a distal substrate binding site. Structural comparison shows that transport of substrates through a tunnel that links the two binding sites, toward an exit portal, is mediated by the conformation of a short 14-aa loop. Taken together, the ZneA structures presented here provide mechanistic insights into the conformational changes required for substrate efflux by RND superfamily transporters.