Abstract
Abstract Transition metals, such as zinc, are essential micronutrients in all organisms, but also
highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for
homeostasis, conferring cellular detoxification and redistribution through transport of these ions
across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass
with the broadest cargo scope, and hence even their topology remains elusive. Here, we present
structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from
Sulfitobacter 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 and
diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including
a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also
establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other
P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for
example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for
homeostasis, conferring cellular detoxification and redistribution through transport of these ions
across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass
with the broadest cargo scope, and hence even their topology remains elusive. Here, we present
structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from
Sulfitobacter 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 and
diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including
a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also
establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other
P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for
example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
| Original language | English |
|---|---|
| Article number | PMID: 34951590 |
| Number of pages | 21 |
| Journal | eLife |
| DOIs | |
| Publication status | Published - 2022 |
Subject classification (UKÄ)
- Biochemistry and Molecular Biology
- Biophysics