Structural basis of ion uptake in copper-transporting P1B-type ATPases
Nina Salustros, Christina Grønberg, Nisansala S. Abeyrathna, Pin Lyu, Fredrik Orädd, Kaituo Wang, Magnus Andersson, Gabriele Meloni, Pontus Gourdon
Abstract
Abstract Copper is essential for living cells, yet toxic at elevated concentrations. Class 1B P-type (P 1B -) 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 P 1B -ATPases, hampering mechanistic understanding. Here, we present structures that reach 2.7 Å resolution of a copper-specific P 1B -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 P 1B -mediated transport, likely applicable also to human P 1B -members.