Tender love and disassembly: How a TLDc domain protein breaks the V-ATPase.
Tender love and disassembly: How a TLDc domain protein breaks the V-ATPase.
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温柔的爱与拆卸：TLDc 结构域蛋白如何破坏 V-ATP 酶。
DOI：
10.1002/bies.202200251
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Oot,RebeccaA
中科院分区：
文献类型：
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作者：
Wilkens,Stephan;Khan,MdMurad;Knight,Kassidy;Oot,RebeccaA
液泡ATPase(V-ATPase，V1Vo-ATPase)是一种旋转马达质子泵，可以酸化细胞内的隔室，当定位于质膜时，也可以酸化细胞外的空间。V-ATPase受一种被称为可逆分解的独特过程的调节，在这种过程中，V1-ATPase响应不同的环境信号而脱离Voproton通道。尽管这一过程的拆解步骤是依赖于ATP的，但(重新)组装步骤并不依赖于ATP，而是需要一种称为RAVE复合体的异三聚体伴侣的作用。最近，人们发现了另一种全酶分解的途径，该途径涉及与氧化应激反应相关的氧化抗性蛋白1(Oxr1p)的结合。与依赖于酶活性的传统可逆解离不同，Oxr1p在没有ATP的情况下可以诱导解离。酵母Oxr1p属于TLDc结构域家族，含有从酵母到哺乳动物都保守的蛋白质，并在多种组织中参与V-ATPase功能。这一简短的观点总结了我们所知道的控制可逆(依赖于ATP)和Oxr1p驱动(不依赖于ATP)的V-ATPase解离为自抑制的V1和Vossubb复合体的分子机制。
Vacuolar ATPases (V‐ATPases, V1Vo‐ATPases) are rotary motor proton pumps that acidify intracellular compartments, and, when localized to the plasma membrane, the extracellular space. V‐ATPase is regulated by a unique process referred to asreversible disassembly, wherein V1‐ATPase disengages from Voproton channel in response to diverse environmental signals. Whereas the disassembly step of this process is ATP dependent, the (re)assembly step is not, but requires the action of a heterotrimeric chaperone referred to as the RAVE complex. Recently, an alternative pathway of holoenzyme disassembly was discovered that involves binding of Oxidation Resistance 1 (Oxr1p), a poorly characterized protein implicated in oxidative stress response. Unlike conventional reversible disassembly, which depends on enzyme activity, Oxr1p induced dissociation can occur in absence of ATP. Yeast Oxr1p belongs to the family of TLDc domain containing proteins that are conserved from yeast to mammals, and have been implicated in V‐ATPase function in a variety of tissues. This brief perspective summarizes what we know about the molecular mechanisms governing both reversible (ATP dependent) and Oxr1p driven (ATP independent) V‐ATPase dissociation into autoinhibited V1and Vosubcomplexes.