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Publication Abstract from PubMed

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 A 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.

Structural basis of ion uptake in copper-transporting P1B-type ATPases.,Salustros N, Gronberg C, Abeyrathna NS, Lyu P, Oradd F, Wang K, Andersson M, Meloni G, Gourdon P Nat Commun. 2022 Aug 31;13(1):5121. doi: 10.1038/s41467-022-32751-w. PMID:36045128^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.