The molecular principles governing the activity and functional diversity of AAA+ proteins.
The molecular principles governing the activity and functional diversity of AAA+ proteins.
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DOI：
10.1038/s41580-019-0183-6
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发表时间：
2020-01
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--
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与多种细胞活性相关的ATP酶（AAA+蛋白）是大分子机器，其将ATP分子中所含的化学能转化为强大的机械力，以重塑大量细胞基质，包括蛋白质聚集体、大分子复合物和聚合物。AAA+蛋白具有关键的功能，包括在不同的亚细胞定位中展开和分解这些底物，因此，为大量的基本细胞过程提供动力，包括蛋白质质量控制，细胞骨架重塑和膜动力学。在过去的35年里，AAA+活性所需的许多关键元素已经通过遗传，生物化学和结构分析确定。然而，ATP如何驱动底物重塑以及AAA+超家族的功能多样性是否存在共享机制尚不确定。冷冻电子显微镜的进步使AAA+蛋白质的高分辨率结构测定成为可能，这些蛋白质被困在处理底物的过程中，揭示了保守的核心作用机制。同样显而易见的是，这种常见的机械原理在结构上进行了调整，以执行各种各样的生物功能。在这里，我们回顾AAA+蛋白质的底物结合结构如何扩大了我们对ATP驱动的蛋白质重塑的理解。
ATPases associated with diverse cellular activities (AAA+ proteins) are macromolecular machines that convert the chemical energy contained in ATP molecules into powerful mechanical forces to remodel a vast array of cellular substrates, including protein aggregates, macromolecular complexes and polymers. AAA+ proteins have key functionalities encompassing unfolding and disassembly of such substrates in different subcellular localizations and, hence, power a plethora of fundamental cellular processes, including protein quality control, cytoskeleton remodelling and membrane dynamics. Over the past 35 years, many of the key elements required for AAA+ activity have been identified through genetic, biochemical and structural analyses. However, how ATP powers substrate remodelling and whether a shared mechanism underlies the functional diversity of the AAA+ superfamily were uncertain. Advances in cryo-electron microscopy have enabled high-resolution structure determination of AAA+ proteins trapped in the act of processing substrates, revealing a conserved core mechanism of action. It has also become apparent that this common mechanistic principle is structurally adjusted to carry out a diverse array of biological functions. Here, we review how substrate-bound structures of AAA+ proteins have expanded our understanding of ATP-driven protein remodelling.
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影响因子：
16
作者：
Augustin, Steffen;Gerdes, Florian;Lee, Sukyeong;Tsai, Francis T. F.;Langer, Thomas;Tatsuta, Takashi
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