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Structure of V-ATPase from the mammalian brain.

ABSTRACT: 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.

SUBMITTER: Abbas YM

PROVIDER: S-EPMC7324285 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Structure of V-ATPase from the mammalian brain.

Abbas Yazan M YM Wu Di D Bueler Stephanie A SA Robinson Carol V CV Rubinstein John L JL

Science (New York, N.Y.) 20200301 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 ...[more]

PMID: 32165585

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