一个 Zpr1 共伴侣通过 GTP 酶循环介导真核翻译延伸因子 1A 的折叠。
A Zpr1 co-chaperone mediates folding of eukaryotic translation elongation factor 1A via a GTPase cycle.
机构信息
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
出版信息
Mol Cell. 2023 Sep 7;83(17):3108-3122.e13. doi: 10.1016/j.molcel.2023.07.028. Epub 2023 Aug 18.
General protein folding is mediated by chaperones that utilize ATP hydrolysis to regulate client binding and release. Zinc-finger protein 1 (Zpr1) is an essential ATP-independent chaperone dedicated to the biogenesis of eukaryotic translation elongation factor 1A (eEF1A), a highly abundant GTP-binding protein. How Zpr1-mediated folding is regulated to ensure rapid Zpr1 recycling remains an unanswered question. Here, we use yeast genetics and microscopy analysis, biochemical reconstitution, and structural modeling to reveal that folding of eEF1A by Zpr1 requires GTP hydrolysis. Furthermore, we identify the highly conserved altered inheritance of mitochondria 29 (Aim29) protein as a Zpr1 co-chaperone that recognizes eEF1A in the GTP-bound, pre-hydrolysis conformation. This interaction dampens Zpr1⋅eEF1A GTPase activity and facilitates client exit from the folding cycle. Our work reveals that a bespoke ATP-independent chaperone system has mechanistic similarity to ATPase chaperones but unexpectedly relies on client GTP hydrolysis to regulate the chaperone-client interaction.
一般蛋白质折叠是由伴侣分子介导的，伴侣分子利用 ATP 水解来调节客户蛋白的结合和释放。锌指蛋白 1（Zpr1）是一种必需的、ATP 非依赖性伴侣分子，专门用于真核翻译延伸因子 1A（eEF1A）的生物发生，eEF1A 是一种高度丰富的 GTP 结合蛋白。Zpr1 介导的折叠如何被调节以确保快速的 Zpr1 循环回收仍然是一个未解决的问题。在这里，我们使用酵母遗传学和显微镜分析、生化重构和结构建模来揭示 Zpr1 折叠 eEF1A 需要 GTP 水解。此外，我们确定高度保守的线粒体 29（Aim29）蛋白作为 Zpr1 的共伴侣，它识别 GTP 结合、预水解构象中的 eEF1A。这种相互作用抑制了 Zpr1·eEF1A GTPase 活性，并促进了客户蛋白从折叠循环中释放。我们的工作表明，一种定制的 ATP 非依赖性伴侣分子系统与 ATP 酶伴侣分子具有相似的机制，但出人意料的是，它依赖于客户 GTP 水解来调节伴侣分子-客户蛋白的相互作用。
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