Structure and ion-release mechanism of P IB-4-type ATPases
(2022) In eLife- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/975c5e6d-df96-471b-9f67-dbe07791f8a3
- author
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- eLife
- article number
- PMID: 34951590
- pages
- 21 pages
- publisher
- eLife Sciences Publications
- external identifiers
-
- pmid:34951590
- scopus:85122387723
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.73124
- language
- English
- LU publication?
- yes
- id
- 975c5e6d-df96-471b-9f67-dbe07791f8a3
- date added to LUP
- 2022-03-24 15:37:17
- date last changed
- 2023-09-12 10:45:32
@article{975c5e6d-df96-471b-9f67-dbe07791f8a3, abstract = {{Abstract Transition metals, such as zinc, are essential micronutrients in all organisms, but also<br/>highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for<br/>homeostasis, conferring cellular detoxification and redistribution through transport of these ions<br/>across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass<br/>with the broadest cargo scope, and hence even their topology remains elusive. Here, we present<br/>structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from<br/>Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-<br/>metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism and<br/>diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including<br/>a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also<br/>establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other<br/>P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for<br/>example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.}}, author = {{Grønberg, Christina and Hu, Qiaoxia and Ram Mahato, Dhani and Longhin, Elena and Salustros, Nina and Duelli, Annette and Lyu, Pin and Bågenholm, Viktoria and Eriksson, Jonas and Umashankar Rao, Komal and Henderson, Domhnall Iain and Meloni, Gabriele and Andersson, Magnus and Croll, Tristan and Godaly, Gabriela and Wang, Kaituo and Gourdon, Pontus}}, issn = {{2050-084X}}, language = {{eng}}, publisher = {{eLife Sciences Publications}}, series = {{eLife}}, title = {{Structure and ion-release mechanism of P IB-4-type ATPases}}, url = {{http://dx.doi.org/10.7554/eLife.73124}}, doi = {{10.7554/eLife.73124}}, year = {{2022}}, }