Finley Daniel
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Annu Rev Biochem. 2009;78:477-513. doi: 10.1146/annurev.biochem.78.081507.101607.
The proteasome is an intricate molecular machine, which serves to degrade proteins following their conjugation to ubiquitin. Substrates dock onto the proteasome at its 19-subunit regulatory particle via a diverse set of ubiquitin receptors and are then translocated into an internal chamber within the 28-subunit proteolytic core particle (CP), where they are hydrolyzed. Substrate is threaded into the CP through a narrow gated channel, and thus translocation requires unfolding of the substrate. Six distinct ATPases in the regulatory particle appear to form a ring complex and to drive unfolding as well as translocation. ATP-dependent, degradation-coupled deubiquitination of the substrate is required both for efficient substrate degradation and for preventing the degradation of the ubiquitin tag. However, the proteasome also contains deubiquitinating enzymes (DUBs) that can remove ubiquitin before substrate degradation initiates, thus allowing some substrates to dissociate from the proteasome and escape degradation. Here we examine the key elements of this molecular machine and how they cooperate in the processing of proteolytic substrates.
蛋白酶体是一种复杂的分子机器，其作用是在蛋白质与泛素结合后将其降解。底物通过多种泛素受体停靠在蛋白酶体的19亚基调节颗粒上，然后被转运到28亚基蛋白水解核心颗粒（CP）的内部腔室中，在那里它们被水解。底物通过一个狭窄的门控通道穿入CP，因此转运需要底物展开。调节颗粒中的六种不同的ATP酶似乎形成一个环状复合物，并驱动展开和转运。底物的ATP依赖性、与降解偶联的去泛素化对于有效的底物降解和防止泛素标签的降解都是必需的。然而，蛋白酶体也含有去泛素化酶（DUBs），它们可以在底物降解开始之前去除泛素，从而使一些底物能够从蛋白酶体上解离并逃脱降解。在这里，我们研究了这个分子机器的关键元件以及它们在蛋白水解底物加工过程中的协作方式。
