Structure and Mechanism of P-Type ATPase Ion Pumps.

P-type ATPases are found in all kingdoms of life and constitute a wide range of cation transporters, primarily for H⁺, Na⁺, K⁺, Ca²⁺, and transition metal ions such as Cu(I), Zn(II), and Cd(II). They have been studied through a wide range of techniques, and research has gained very significant insight on their transport mechanism and regulation. Here, we review the structure, function, and dynamics of P2-ATPases including Ca²⁺-ATPases and Na,K-ATPase. We highlight mechanisms of functional transitions that are associated with ion exchange on either side of the membrane and how the functional cycle is regulated by interaction partners, autoregulatory domains, and off-cycle states. Finally, we discuss future perspectives based on emerging techniques and insights.