Zongxin Guo, Fredrik Orädd, Viktoria Bågenholm, Christina Grønberg, Jian Feng Ma, Peter Ott, Yong Wang, Magnus Andersson, Per Amstrup Pedersen, Kaituo Wang, Pontus Gourdon
Copper transporting P-type (P1B-1 -) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1 -ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1 -ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD-1 , serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD-1 , MBD-2 , likely assists in copper delivery to the ATPase core...
March 27, 2024: Nature Communications