Structure of V-ATPase from the mammalian brain

Science. 2020 Mar 13;367(6483):1240-1246. doi: 10.1126/science.aaz2924.


In neurons, the loading of neurotransmitters into synaptic vesicles uses energy from proton-pumping vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases). These membrane protein complexes possess numerous subunit isoforms, which complicates their analysis. We isolated homogeneous rat brain V-ATPase through its interaction with SidK, a Legionella pneumophila effector protein. Cryo-electron microscopy allowed the construction of an atomic model, defining the enzyme's ATP:proton ratio as 3:10 and revealing a homolog of yeast subunit f in the membrane region, which we tentatively identify as RNAseK. The c ring encloses the transmembrane anchors for cleaved ATP6AP1/Ac45 and ATP6AP2/PRR, the latter of which is the (pro)renin receptor that, in other contexts, is involved in both Wnt signaling and the renin-angiotensin system that regulates blood pressure. This structure shows how ATP6AP1/Ac45 and ATP6AP2/PRR enable assembly of the enzyme's catalytic and membrane regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Biocatalysis
  • Biomarkers / chemistry*
  • Brain / enzymology*
  • Cell Membrane / enzymology
  • Cryoelectron Microscopy
  • Models, Chemical
  • Protein Domains
  • Rats
  • Receptors, Cell Surface / chemistry*
  • Renin-Angiotensin System
  • Vacuolar Proton-Translocating ATPases / chemistry*
  • Wnt Signaling Pathway


  • Atp6ap1 protein, rat
  • Bacterial Proteins
  • Biomarkers
  • Receptors, Cell Surface
  • ATP6AP2 protein, rat
  • Vacuolar Proton-Translocating ATPases