4UMW: Crystal Structure Of A Zinc-transporting Pib-type Atpase In E2.pi State

Citation:
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 A and 2.7 A 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.
PDB ID: 4UMWDownload
MMDB ID: 122442
PDB Deposition Date: 2014/5/21
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4UMW: monomeric; determined by author and by software (PISA)
Molecular Components in 4UMW
Label Count Molecule
Protein (1 molecule)
1
Zinc-transporting Atpase
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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