Structure and Mechanism of P-Type ATPase Ion Pumps

Annu Rev Biochem. 2020 Jun 20;89:583-603. doi: 10.1146/annurev-biochem-010611-112801. Epub 2020 Dec 24.


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.

Keywords: Ca2+-ATPase; Na,K-ATPase; autoinhibition; intrinsically disordered; membrane transport protein; single molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Cations, Divalent
  • Cations, Monovalent
  • Copper-Transporting ATPases / chemistry*
  • Copper-Transporting ATPases / genetics
  • Copper-Transporting ATPases / metabolism
  • H(+)-K(+)-Exchanging ATPase / chemistry*
  • H(+)-K(+)-Exchanging ATPase / genetics
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Humans
  • Ion Transport
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Protons
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / chemistry*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Single Molecule Imaging
  • Sodium-Potassium-Exchanging ATPase / chemistry*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Substrate Specificity


  • Cations, Divalent
  • Cations, Monovalent
  • Protons
  • Adenosine Triphosphate
  • H(+)-K(+)-Exchanging ATPase
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Sodium-Potassium-Exchanging ATPase
  • Copper-Transporting ATPases