biostudies-literatureAbbas YMEuropean Research CouncilThe Hospital For Sick ChildrenWellcome TrustCanadian Institutes of Health ResearchCIHRCanada Research Chairs1240-1246https://www.ebi.ac.uk/biostudies/studies/S-EPMC7324285biostudies-literatureUnknown367(6483)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 <i>Legionella pneumophila</i> 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 botScience (New York, N.Y.)Structure of V-ATPase from the mammalian brain.PMC7324285695511PJT166152104633/Z/14/Z104633Postdoctoral Fellowship69551-ENABLEAbbas YMRubinstein JLBueler SAWu DRobinson CVfalseStructure of V-ATPase from the mammalian brain.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 <i>Legionella pneumophila</i> 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 bot2020-01-01T00:00:00Z2020 Mar2026-05-03T04:48:47.272Z2020-09-15T07:23:23ZS-EPMC73242853216558510.1126/science.aaz2924