TY - JOUR

T1 - Structural basis of ion uptake in copper-transporting P1B-type ATPases

AU - Salustros, Nina

AU - Gronberg, Christina

AU - Abeyrathna, Nisansala S.

AU - Lyu, Pin

AU - Oradd, Fredrik

AU - Wang, Kaituo

AU - Andersson, Magnus

AU - Meloni, Gabriele

AU - Gourdon, Pontus

PY - 2022

Y1 - 2022

N2 - P-1B-type ATPases export excess transition metals from cells. Here, the authors report a molecular structure of CopA, a coppertransporting P-1B-ATPase from A. fulgidus, in an inward-facing E1 conformation.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 angstrom 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.

AB - P-1B-type ATPases export excess transition metals from cells. Here, the authors report a molecular structure of CopA, a coppertransporting P-1B-ATPase from A. fulgidus, in an inward-facing E1 conformation.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 angstrom 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.

KW - METAL-BINDING DOMAINS

KW - MOLECULAR-DYNAMICS

KW - CU+

KW - MECHANISM

KW - PUMP

KW - PHOSPHATE

KW - SITES

KW - COPA

U2 - 10.1038/s41467-022-32751-w

DO - 10.1038/s41467-022-32751-w

M3 - Journal article

C2 - 36045128

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5121

ER -