Fig. 3. The diverse functional roles of the metal binding domains (MBDs).

A Functional data comparing wildtype human ATP7B and truncations with no MBD (Δ(MBD⁻⁶-MBD⁻¹)ATP7B) or only MBD⁻¹ (Δ(MBD⁻⁶-MBD⁻¹)ATP7B) attached to the ATPase core. Assessed through detection of released inorganic phosphate in detergent solution as triggered by copper and ATP in triplicate (n = 3 distinct biochemical samples). Data are presented as averages with standard deviation error bars. See also Supplementary Fig. 2. B Structural comparison of the cytoplasmic domains of the E2P (XtATP7B) and E1 states (HMA4^apo) suggests the E2P → E1 transition can occur without MBD⁻² interference. View from the cytoplasm. C Structural comparison of the E1 (as shown in panel D) and E2P states (as shown in panel E) suggests the E1 → E2P transition cannot occur without interference of MBD⁻³ when located at the suggested position. View from the cytoplasm. D MD simulations of the E1 state (HMBA^apo) indicates MBD⁻² is stable at the MB’ platform, while the MBD preceding MBD⁻², MBD⁻³, is flexible, but can interact with the ATPase core at the A-/P-domain interface. Cysteines of the CXXC motifs shown as spheres. See also Supplementary Fig. 19. E, F MD simulations of the E2P state (HMBA^AlF) imply MBD⁻² is dynamic and can interact with the ATPase core at the A-/P-domain interface (panel D) and at the MB’ platform (panel E). Cysteines of the CXXC motifs shown as spheres in both panels. See also Supplementary Fig. 19.