4K0J

X-ray crystal structure of a heavy metal efflux pump, crystal form I

Summary for 4K0J

• Entry DOI: 10.2210/pdb4k0j/pdb
• Related: 4K0E
• Descriptor: Heavy metal cation tricomponent efflux pump ZneA(CzcA-like), ZINC ION (2 entities in total)
• Functional Keywords: structural genomics, psi-biology, center for structures of membrane proteins, csmp, resistance-nodulation-cell division (rnd) superfamily, heavy metal efflux pump, zneb, znec, inner membrane, transport protein
• Biological source: Cupriavidus metallidurans
• Total number of polymer chains: 6
• Total formula weight: 687448.15

Authors

Pak, J.E.,Stroud, R.M.,Ngonlong Ekende, E.,Vandenbussche, G.,Center for Structures of Membrane Proteins (CSMP) (deposition date: 2013-04-04, release date: 2013-10-16, Last modification date: 2023-09-20)

Primary citation

Pak, J.E.,Ekende, E.N.,Kifle, E.G.,O'Connell, J.D.,De Angelis, F.,Tessema, M.B.,Derfoufi, K.M.,Robles-Colmenares, Y.,Robbins, R.A.,Goormaghtigh, E.,Vandenbussche, G.,Stroud, R.M.
Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter.
Proc.Natl.Acad.Sci.USA, 110:18484-18489, 2013

PubMed 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.

PubMed: 24173033
DOI: 10.1073/pnas.1318705110

Experimental method

X-RAY DIFFRACTION (3 Å)