Structural basis of ion uptake in copper-transporting P1B-type ATPases
(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
- Salustros, Nina ; Grønberg, Christina ; Abeyrathna, Nisansala S. ; Lyu, Pin ; Orädd, Fredrik ; Wang, Kaituo ; Andersson, Magnus ; Meloni, Gabriele and Gourdon, Pontus LU
- organization
- publishing date
- 2022-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 5121
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85137055943
- pmid:36045128
- 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
- 2024-06-27 13:58:40
@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}}, }