Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases.

ABSTRACT: Copper transporting P-type (P_1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P_1B-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 P_1B-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. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, al

SUBMITTER: Guo Z 

PROVIDER: S-EPMC10973460 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature