4UMW

CRYSTAL STRUCTURE OF A ZINC-TRANSPORTING PIB-TYPE ATPASE IN E2.PI STATE

Summary for 4UMW

• Entry DOI: 10.2210/pdb4umw/pdb
• Related: 4UMV
• Descriptor: ZINC-TRANSPORTING ATPASE, TETRAFLUOROALUMINATE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cpc, cxxc, atp-binding, hydrolase, ion transport, magnesium, zn2+, metal-binding, nucleotide-binding, transmembrane, transport, heavy-metal binding, p-type atpase, pib-atpase, zn2+ exporting, zinc transport, pi-atpase, membrane protein
• Biological source: SHIGELLA SONNEI
• Total number of polymer chains: 1
• Total formula weight: 76968.79

Authors

Wang, K.T.,Sitsel, O.,Meloni, G.,Autzen, H.E.,Andersson, M.,Klymchuk, T.,Nielsen, A.M.,Rees, D.C.,Nissen, P.,Gourdon, P. (deposition date: 2014-05-21, release date: 2014-08-13, Last modification date: 2024-01-10)

Primary citation

Wang, K.,Sitsel, O.,Meloni, G.,Autzen, H.E.,Andersson, M.,Klymchuk, T.,Nielsen, A.M.,Rees, D.C.,Nissen, P.,Gourdon, P.
Structure and Mechanism of Zn(2+)-Transporting P-Type Atpases.
Nature, 514:518-, 2014

PubMed 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.

PubMed: 25132545
DOI: 10.1038/NATURE13618

Experimental method

X-RAY DIFFRACTION (2.705 Å)