Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Nat Commun. 2013;4:2234. doi: 10.1038/ncomms3234.
The 26S proteasome has an elaborate structure, consisting of 33 different subunits that form the 20S core particle capped by the 19S regulatory particle on either end. Several chaperones that are dedicated to the accurate assembly of this protease complex have been identified, but the mechanisms underlying proteasome biogenesis remain unexplored so far. Here we report that core particle assembly becomes less efficient if the TRC pathway, which mediates insertion of tail-anchored proteins, is defective. We demonstrate that Bag6, a protein in the TRC pathway that is also responsible for the degradation of mislocalized proteins, is not only involved in core particle assembly but also has a key role in efficient regulatory particle assembly by directly associating with precursor regulatory particles. These findings indicate that proteasome assembly is not solely mediated by dedicated chaperones but also depends on general chaperones that preserve protein homeostasis.
26S 蛋白酶体具有精细的结构，由 33 个不同的亚基组成，这些亚基形成 20S 核心颗粒，两端分别由 19S 调节颗粒覆盖。已经鉴定出几种专门用于准确组装这种蛋白酶复合物的伴侣蛋白，但迄今为止，蛋白酶体生物发生的机制仍未被探索。在这里，我们报告说，如果介导尾部锚定蛋白插入的 TRC 途径有缺陷，核心颗粒的组装效率会降低。我们证明，TRC 途径中的 Bag6 蛋白不仅参与核心颗粒的组装，而且还通过直接与前体调节颗粒结合，在有效调节颗粒组装中起着关键作用。这些发现表明，蛋白酶体的组装不仅由专门的伴侣蛋白介导，而且还依赖于维持蛋白质平衡的一般伴侣蛋白。
