Structure 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 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.

Source: ScienceNOW - March 11, 2020 Category: Science Authors: Abbas, Y. M., Wu, D., Bueler, S. A., Robinson, C. V., Rubinstein, J. L. Tags: Biochemistry reports Source Type: news