Le Tallec Benoît, Barrault Marie-Bénédicte, Guérois Raphaël, Carré Thibault, Peyroche Anne
Laboratoire du Métabolisme de l'ADN et Réponses aux Génotoxiques, SBIGeM, CEA, iBiTecS, Gif-sur-Yvette, F-91191, France.
Mol Cell. 2009 Feb 13;33(3):389-99. doi: 10.1016/j.molcel.2009.01.010.
The 26S proteasome, the central enzyme of the ubiquitin-proteasome system, is comprised of the 20S catalytic core particle (CP) and the 19S regulatory particle (RP), itself composed of two subcomplexes, the base and the lid. 20S proteasome assembly is assisted by several chaperones. Integral subunits of the RP participate in its assembly, but no external factors have been identified so far. Here we characterize the yeast Hsm3 protein, which displays unique features regarding 19S assembly. Hsm3 associates with 19S subcomplexes via a carboxy-terminal domain of the Rpt1 base subunit but is missing in the final 26S proteasome. Moreover, Hsm3 is specifically required for the base subcomplex assembly. Finally, we identify the putative species-specific 19S subunit S5b as a functional homolog of the Hsm3 chaperone in mammals. These findings shed light on chaperone-assisted proteasome assembly in eukaryotes.
26S蛋白酶体是泛素-蛋白酶体系统的核心酶，由20S催化核心颗粒（CP）和19S调节颗粒（RP）组成，19S调节颗粒本身又由两个亚复合物，即底座和盖子组成。20S蛋白酶体的组装由几种分子伴侣协助。RP的整合亚基参与其组装，但迄今为止尚未发现外部因素。在这里，我们对酵母Hsm3蛋白进行了表征，该蛋白在19S组装方面具有独特特征。Hsm3通过Rpt1底座亚基的羧基末端结构域与19S亚复合物结合，但在最终的26S蛋白酶体中缺失。此外，Hsm3是底座亚复合物组装所特需的。最后，我们确定推定的物种特异性19S亚基S5b是哺乳动物中Hsm3分子伴侣的功能同源物。这些发现揭示了真核生物中分子伴侣辅助的蛋白酶体组装过程。
