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Structural basis of ion uptake in copper-transporting P1B-type ATPases

Salustros, Nina ; Grønberg, Christina ; Abeyrathna, Nisansala S. ; Lyu, Pin ; Orädd, Fredrik ; Wang, Kaituo ; Andersson, Magnus ; Meloni, Gabriele and Gourdon, Pontus LU (2022) In Nature Communications 13(1).
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... (More)

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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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
13
issue
1
article number
5121
publisher
Nature Publishing Group
external identifiers
  • pmid:36045128
  • scopus:85137055943
ISSN
2041-1723
DOI
10.1038/s41467-022-32751-w
language
English
LU publication?
yes
id
23b7987b-93f7-4673-bc6f-1e64f45f0e2d
date added to LUP
2022-11-08 14:40:39
date last changed
2024-04-18 07:26:05
@article{23b7987b-93f7-4673-bc6f-1e64f45f0e2d,
  abstract     = {{<p>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.</p>}},
  author       = {{Salustros, Nina and Grønberg, Christina and Abeyrathna, Nisansala S. and Lyu, Pin and Orädd, Fredrik and Wang, Kaituo and Andersson, Magnus and Meloni, Gabriele and Gourdon, Pontus}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Structural basis of ion uptake in copper-transporting P<sub>1B</sub>-type ATPases}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-32751-w}},
  doi          = {{10.1038/s41467-022-32751-w}},
  volume       = {{13}},
  year         = {{2022}},
}