Structure of V-ATPase from the mammalian brain
Structure of V-ATPase from the mammalian brain
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DOI：
10.1126/science.aaz2924
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发表时间：
2020-03-13
期刊：
影响因子：
56.9
通讯作者：
Rubinstein, John L.
中科院分区：
文献类型：
--
作者：
Abbas, Yazan M.;Wu, Di;Rubinstein, John L.
在神经元中，将神经递质加载到突触囊泡中使用来自质子泵囊泡或空泡型腺苷三磷酸酶（V-ATP酶）的能量。这些膜蛋白复合物具有许多亚基同种型，这使它们的分析复杂化。我们通过与嗜肺军团菌效应蛋白SidK的相互作用分离了同质的大鼠脑V-ATP酶。冷冻电子显微镜允许构建原子模型，将酶的ATP：质子比定义为3：10，并揭示了膜区域中酵母亚基f的同源物，我们暂时将其鉴定为RNAseK。c环包围切割的ATP 6AP 1/Ac 45和ATP 6AP 2/PRR的跨膜锚定物，后者是（原）肾素受体，在其他情况下，其参与Wnt信号传导和调节血压的肾素-血管紧张素系统。该结构显示了ATP 6AP 1/Ac 45和ATP 6AP 2/PRR如何能够组装酶的催化和膜区域。
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. Cryoelectron 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.