Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase

Science. 2019 Aug 23;365(6455):eaaw9144. doi: 10.1126/science.aaw9144.


V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found in archaea and eubacteria, couple ATP hydrolysis or synthesis to proton translocation across the plasma membrane using the rotary-catalysis mechanism. They belong to the V-type ATPase family, which differs from the mitochondrial/chloroplast F-type ATP synthases in overall architecture. We solved cryo-electron microscopy structures of the intact Thermus thermophilus V/A-ATPase, reconstituted into lipid nanodiscs, in three rotational states and two substates. These structures indicate substantial flexibility between V1 and Vo in a working enzyme, which results from mechanical competition between central shaft rotation and resistance from the peripheral stalks. We also describe details of adenosine diphosphate inhibition release, V1-Vo torque transmission, and proton translocation, which are relevant for the entire V-type ATPase family.

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Bacterial Proteins / chemistry*
  • Catalysis
  • Cryoelectron Microscopy
  • Mitochondrial Proton-Translocating ATPases / chemistry
  • Models, Chemical
  • Nanoparticles / chemistry
  • Phylogeny
  • Protein Domains
  • Protein Multimerization
  • Substrate Specificity
  • Thermus thermophilus / enzymology*
  • Vacuolar Proton-Translocating ATPases / antagonists & inhibitors
  • Vacuolar Proton-Translocating ATPases / chemistry*
  • Vacuolar Proton-Translocating ATPases / classification


  • Bacterial Proteins
  • Adenosine Diphosphate
  • Vacuolar Proton-Translocating ATPases
  • Mitochondrial Proton-Translocating ATPases