Structure of V-ATPase from the mammalian brain

Journal article

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.

Authors: Abbas, YM; Wu, D; Bueler, SA; Robinson, CV; Rubinstein, JL

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science
• Volume: 367
• Issue: 6483
• Pages: 1240-1246
• Publication date: 2020-03-13
• Acceptance date: 2020-02-12
• DOI: 10.1126/science.aaz2924
• EISSN: 1095-9203
• ISSN: 0036-8075
• Pmid: 32165585
• Language: English
• Keywords: bacterial proteins; cell membrane; Wnt Signaling Pathway; rats; FFR; biocatalysis; animals; Renin-Angiotensin System; vacuolar proton-translocating ATPases; biomarkers; brain; receptors, cell surface; models, chemical; protein domains; cryoelectron microscopy