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Structure and ion-release mechanism of P IB-4-type ATPases

Grønberg, Christina ; Hu, Qiaoxia ; Ram Mahato, Dhani ; Longhin, Elena ; Salustros, Nina ; Duelli, Annette ; Lyu, Pin ; Bågenholm, Viktoria LU ; Eriksson, Jonas and Umashankar Rao, Komal LU , et al. (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)
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organization
publishing date
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}},
}