Structure and ion-release mechanism of PIB-4-type ATPases.
Authors
Grønberg, Christina
Hu, Qiaoxia
Longhin, Elena
Salustros, Nina
Duelli, Annette
Bågenholm, Viktoria
Eriksson, Jonas
Rao, Komal Umashankar
Henderson, Domhnall Iain
Croll, Tristan
Wang, Kaituo
Publication Date
2021-12-24Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
10
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Grønberg, C., Hu, Q., Mahato, D. R., Longhin, E., Salustros, N., Duelli, A., Lyu, P., et al. (2021). Structure and ion-release mechanism of PIB-4-type ATPases.. Elife, 10 https://doi.org/10.7554/eLife.73124
Description
Funder: The memorial foundation of manufacturer Vilhelm Pedersen and wife - and the Aarhus Wilson consortium
Funder: China Scholarship Council; FundRef: http://dx.doi.org/10.13039/501100004543
Funder: Carl Tryggers Stiftelse för Vetenskaplig Forskning; FundRef: http://dx.doi.org/10.13039/501100002805; Grant(s): CTS 17:22
Funder: Agnes og Poul Friis Fond; FundRef: http://dx.doi.org/10.13039/100009512
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.
Keywords
Research Article, Biochemistry and Chemical Biology, Structural Biology and Molecular Biophysics, P-type ATPase, x-ray crystallography, sulfitobacter sp. NAS14-1, transition metals, PIB-4-ATPase, Other
Sponsorship
Wellcome Trust (209407/Z/17/Z)
Identifiers
73124
External DOI: https://doi.org/10.7554/eLife.73124
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334474
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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