Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18484-9. doi: 10.1073/pnas.1318705110. Epub 2013 Oct 30.

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

Author information

1
Department of Biochemistry and Biophysics, Center for the Structure of Membrane Proteins, Membrane Protein Expression Center, University of California, San Francisco, CA 94158.

Abstract

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.

PMID:
24173033
PMCID:
PMC3832018
DOI:
10.1073/pnas.1318705110
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center