Structure and mechanism of Zn(2+)-transporting P-type ATPases.
(2014) In Nature- 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 Å and 2.7 Å resolution, respectively. The structures reveal a similar fold to Cu(+)-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel... (More)
- 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 Å and 2.7 Å 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4614425
- author
- Wang, Kaituo ; Sitsel, Oleg ; Meloni, Gabriele ; Autzen, Henriette Elisabeth ; Andersson, Magnus ; Klymchuk, Tetyana ; Nielsen, Anna Marie ; Rees, Douglas C ; Nissen, Poul and Gourdon, Pontus LU
- organization
- publishing date
- 2014-08-17
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:25132545
- wos:000343775900046
- scopus:84925941003
- pmid:25132545
- ISSN
- 0028-0836
- DOI
- 10.1038/nature13618
- language
- English
- LU publication?
- yes
- id
- 7c05015f-f56a-4aeb-8aaf-9ed940b44e07 (old id 4614425)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25132545?dopt=Abstract
- date added to LUP
- 2016-04-04 08:53:56
- date last changed
- 2022-03-15 08:51:13
@article{7c05015f-f56a-4aeb-8aaf-9ed940b44e07,
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 Å and 2.7 Å 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 = {{Wang, Kaituo and Sitsel, Oleg and Meloni, Gabriele and Autzen, Henriette Elisabeth and Andersson, Magnus and Klymchuk, Tetyana and Nielsen, Anna Marie and Rees, Douglas C and Nissen, Poul and Gourdon, Pontus}},
issn = {{0028-0836}},
language = {{eng}},
month = {{08}},
publisher = {{Nature Publishing Group}},
series = {{Nature}},
title = {{Structure and mechanism of Zn(2+)-transporting P-type ATPases.}},
url = {{http://dx.doi.org/10.1038/nature13618}},
doi = {{10.1038/nature13618}},
year = {{2014}},
}