| 1. |
- Grønberg, Christina, et al.
(författare)
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Structure and ion-release mechanism of P IB-4-type ATPases
- 2022
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Transition metals, such as zinc, are essential micronutrients in all organisms, but alsohighly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial forhomeostasis, conferring cellular detoxification and redistribution through transport of these ionsacross cellular membranes. No structural information is available for the PIB-4-ATPases, the subclasswith the broadest cargo scope, and hence even their topology remains elusive. Here, we presentstructures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT fromSulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism anddiversity of heavy-metal transporters. We reveal several novel P-type ATPase features, includinga dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We alsoestablish that the turnover of PIB-ATPases is potassium independent, contrasting to many otherP-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in forexample drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
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| 2. |
- Salustros, Nina, et al.
(författare)
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Structural basis of ion uptake in copper-transporting P1B-type ATPases
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Copper is essential for living cells, yet toxic at elevated concentrations. Class 1B P-type (P1B-) ATPases are present in all kingdoms of life, facilitating cellular export of transition metals including copper. P-type ATPases follow an alternating access mechanism, with inward-facing E1 and outward-facing E2 conformations. Nevertheless, no structural information on E1 states is available for P1B-ATPases, hampering mechanistic understanding. Here, we present structures that reach 2.7 Å resolution of a copper-specific P1B-ATPase in an E1 conformation, with complementing data and analyses. Our efforts reveal a domain arrangement that generates space for interaction with ion donating chaperones, and suggest a direct Cu+ transfer to the transmembrane core. A methionine serves a key role by assisting the release of the chaperone-bound ion and forming a cargo entry site together with the cysteines of the CPC signature motif. Collectively, the findings provide insights into P1B-mediated transport, likely applicable also to human P1B-members.
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