Structure and mechanism of Zn2+-transporting P-type ATPases

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Structure and mechanism of Zn2+-transporting P-type ATPases. / Wang, Kaituo; Sitsel, Oleg; Meloni, Gabriele; Autzen, Henriette Elisabeth; Andersson, Magnus; Klymchuk, Tetyana; Nielsen, Anna Marie; Rees, Douglas C; Nissen, Poul; Gourdon, Pontus.

I: Nature, Bind 514, Nr. 7523, 23.10.2014, s. 518-522.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Wang, K, Sitsel, O, Meloni, G, Autzen, HE, Andersson, M, Klymchuk, T, Nielsen, AM, Rees, DC, Nissen, P & Gourdon, P 2014, 'Structure and mechanism of Zn2+-transporting P-type ATPases', Nature, bind 514, nr. 7523, s. 518-522. https://doi.org/10.1038/nature13618

APA

Wang, K., Sitsel, O., Meloni, G., Autzen, H. E., Andersson, M., Klymchuk, T., Nielsen, A. M., Rees, D. C., Nissen, P., & Gourdon, P. (2014). Structure and mechanism of Zn2+-transporting P-type ATPases. Nature, 514(7523), 518-522. https://doi.org/10.1038/nature13618

CBE

Wang K, Sitsel O, Meloni G, Autzen HE, Andersson M, Klymchuk T, Nielsen AM, Rees DC, Nissen P, Gourdon P. 2014. Structure and mechanism of Zn2+-transporting P-type ATPases. Nature. 514(7523):518-522. https://doi.org/10.1038/nature13618

MLA

Vancouver

Wang K, Sitsel O, Meloni G, Autzen HE, Andersson M, Klymchuk T o.a. Structure and mechanism of Zn2+-transporting P-type ATPases. Nature. 2014 okt 23;514(7523):518-522. https://doi.org/10.1038/nature13618

Author

Wang, Kaituo ; Sitsel, Oleg ; Meloni, Gabriele ; Autzen, Henriette Elisabeth ; Andersson, Magnus ; Klymchuk, Tetyana ; Nielsen, Anna Marie ; Rees, Douglas C ; Nissen, Poul ; Gourdon, Pontus. / Structure and mechanism of Zn2+-transporting P-type ATPases. I: Nature. 2014 ; Bind 514, Nr. 7523. s. 518-522.

Bibtex

@article{2bb658de65fb4490a3d49cee7f63c547,
title = "Structure and mechanism of Zn2+-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 catalysis1. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements2, 3. 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 Zn2+ 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 Zn2+ 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 Zn2+-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 Ca2+-ATPase4, 5 (SERCA) and Na+, K+-ATPase6. 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",
month = oct,
day = "23",
doi = "10.1038/nature13618",
language = "English",
volume = "514",
pages = "518--522",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7523",

}

RIS

TY - JOUR

T1 - Structure and mechanism of Zn2+-transporting P-type ATPases

AU - Wang, Kaituo

AU - Sitsel, Oleg

AU - Meloni, Gabriele

AU - Autzen, Henriette Elisabeth

AU - Andersson, Magnus

AU - Klymchuk, Tetyana

AU - Nielsen, Anna Marie

AU - Rees, Douglas C

AU - Nissen, Poul

AU - Gourdon, Pontus

PY - 2014/10/23

Y1 - 2014/10/23

N2 - 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 catalysis1. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements2, 3. 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 Zn2+ 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 Zn2+ 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 Zn2+-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 Ca2+-ATPase4, 5 (SERCA) and Na+, K+-ATPase6. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.

AB - 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 catalysis1. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements2, 3. 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 Zn2+ 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 Zn2+ 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 Zn2+-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 Ca2+-ATPase4, 5 (SERCA) and Na+, K+-ATPase6. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.

U2 - 10.1038/nature13618

DO - 10.1038/nature13618

M3 - Journal article

C2 - 25132545

VL - 514

SP - 518

EP - 522

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7523

ER -