Resolving individual steps in the operation of ATP-dependent proteolytic molecular machines: From conformational changes to substrate translocation and processivity
Resolving individual steps in the operation of ATP-dependent proteolytic molecular machines: From conformational changes to substrate translocation and processivity
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DOI：
10.1021/bi800025g
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发表时间：
2008-03-25
期刊：
影响因子：
2.9
通讯作者：
Lee, Irene
中科院分区：
文献类型：
--
作者：
Licht, Stuart;Lee, Irene
Clp、Lon和FtsH蛋白酶是蛋白水解分子机器，其使用ATP水解的自由能来解折叠蛋白质底物并将其前递呈至蛋白酶活性位点。在这里，我们回顾了最近的生物化学和结构相关的ATP依赖性蛋白水解的机制的研究。尽管Clp、Lon和FtsH蛋白酶之间存在显著的结构差异，但这些酶具有重要的机制特征。在这些系统中，机制研究提供了证据，ATP结合和水解驱动的构象变化，驱动易位的基板，这对蛋白质水解的进行性机制具有重要意义。这些研究表明，ATP酶结合位点的核苷酸（ATP、ADP或不可水解的ATP类似物）占有率可以影响蛋白质底物的结合模式和/或结合亲和力。提出了一个一般的机制，其中ATP酶活性位点和蛋白质底物结合区域之间的通信协调底物结合，易位，蛋白质水解和产物释放的过程性循环。
Clp, Lon, and FtsH proteases are proteolytic molecular machines that use the free energy of ATP hydrolysis to unfold protein substrates and processively present them to protease active sites. Here we review recent biochemical and structural studies relevant to the mechanism of ATP-dependent processive proteolysis. Despite the significant structural differences among the Clp, Lon, and FtsH proteases, these enzymes share important mechanistic features. In these systems, mechanistic studies have provided evidence for ATP binding and hydrolysis-driven conformational changes that drive translocation of substrates, which has significant implications for the processive mechanism of proteolysis. These studies indicate that the nucleotide (ATP, ADP, or nonhydrolyzable ATP analogues) occupancy of the ATPase binding sites can influence the binding mode and/or binding affinity for protein substrates. A general mechanism is proposed in which the communication between ATPase active sites and protein substrate binding regions coordinates a processive cycle of substrate binding, translocation, proteolysis, and product release.