Structure and mechanism of Zn(2+)-transporting P-type ATPases.

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Bibtex

@article{7c05015ff56a4aeb8aaf9ed940b44e07,
title = "Structure and mechanism of Zn(2+)-transporting P-type ATPases.",
abstract = "Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes, Zn(2+)-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn(2+) and related elements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2·Pi) of ZntA from Shigella sonnei, determined at 3.2 {\AA} and 2.7 {\AA} resolution, respectively. The structures reveal a similar fold to Cu(+)-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn(2+) ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2·Pi state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn(2+) release as a built-in counter ion, as has been proposed for H(+)-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between PIB-type Zn(2+)-ATPases and PIII-type H(+)-ATPases and at the same time show structural features of the extracellular release pathway that resemble PII-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+), K(+)-ATPase. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.",
author = "Kaituo Wang and Oleg Sitsel and Gabriele Meloni and Autzen, {Henriette Elisabeth} and Magnus Andersson and Tetyana Klymchuk and Nielsen, {Anna Marie} and Rees, {Douglas C} and Poul Nissen and Pontus Gourdon",
year = "2014",
doi = "10.1038/nature13618",
language = "English",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",

}