QB3 Institute, University of California, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
QB3 Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Trends Biochem Sci. 2014 Feb;39(2):53-60. doi: 10.1016/j.tibs.2013.11.003. Epub 2013 Dec 6.
ATP-dependent proteases exist in all cells and are crucial regulators of the proteome. These machines consist of a hexameric, ring-shaped motor responsible for engaging, unfolding, and translocating protein substrates into an associated peptidase for degradation. Here, we discuss recent work that has established how the six motor subunits coordinate their ATP-hydrolysis and translocation activities. The closed topology of the ring and the rigidity of subunit/subunit interfaces cause conformational changes within a single subunit to drive motions in other subunits of the hexamer. This structural effect generates allostery between the ATP-binding sites, leading to a preferred order of binding and hydrolysis events among the motor subunits as well as a unique biphasic mechanism of translocation.
ATP 依赖的蛋白酶存在于所有细胞中，是蛋白质组的关键调节剂。这些机器由一个六聚体、环形的马达组成，负责结合、展开和转运蛋白质底物进入相关的肽酶进行降解。在这里，我们讨论了最近的工作，这些工作已经确定了六个马达亚基如何协调它们的 ATP 水解和转运活性。环的封闭拓扑结构和亚基/亚基界面的刚性导致单个亚基内的构象变化驱动六聚体中其他亚基的运动。这种结构效应在 ATP 结合位点之间产生变构作用，导致马达亚基之间的结合和水解事件的优先顺序，以及独特的两相转运机制。
