Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis.

Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis.
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DOI:
10.1080/10409238.2021.1979461
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发表时间:
2022-04
影响因子:
6.5
通讯作者:
--
中科院分区:
生物学2区
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--
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ClpXP 是一种典型的 AAA+ 蛋白酶,由 ClpX 和 ClpP 组成。 ClpX 是一种 ATP 依赖性蛋白解折叠酶和多肽转位酶,而 ClpP 是一种自我区室化肽酶。 ClpXP 是目前唯一存在高分辨率结构的 AAA+ 蛋白酶,了解蛋白质底物识别的分子基础,进行了广泛的生化和遗传分析,并且单分子光学捕获允许直接可视化底物解折叠和易位的动力学。在这篇综述中,我们讨论了我们目前对 ClpXP 结构和功能的理解,评估了 ATP 水解的竞争顺序和概率机制,并强调了未来探索的开放问题。
ClpXP is an archetypical AAA+ protease, consisting of ClpX and ClpP. ClpX is an ATP-dependent protein unfoldase and polypeptide translocase, whereas ClpP is a self-compartmentalized peptidase. ClpXP is currently the only AAA+ protease for which high-resolution structures exist, the molecular basis of recognition for a protein substrate is understood, extensive biochemical and genetic analysis have been performed, and single-molecule optical trapping has allowed direct visualization of the kinetics of substrate unfolding and translocation. In this review, we discuss our current understanding of ClpXP structure and function, evaluate competing sequential and probabilistic mechanisms of ATP hydrolysis, and highlight open questions for future exploration.
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