Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany.
Biochem Soc Trans. 2010 Feb;38(Pt 1):29-33. doi: 10.1042/BST0380029.
The 26S proteasome is a non-lysosomal protease in the cytosol and nucleus of eukaryotic cells. Its main function is to mediate ubiquitin-dependent proteolysis. The 26S proteasome is a multimeric complex composed by the 20S proteasome CP (core particle) and the 19S RPs (regulatory particles). Although the atomic structure of the 26S proteasome has not yet been determined, high-resolution structures are available for its CP. Studies on the complicated assembly pathway of the proteasome have revealed that it involves an unprecedented number of dedicated chaperones. Assembly of the CP alone involves three conserved proteasome-assembly chaperones [PAC1-PAC2, PAC3-PAC4 and UMP1 (ubiquitin-mediated proteolysis 1)]. Whereas the two heterodimeric PACs have been implicated in the formation of rings of the seven distinct alpha subunits, UMP1 is important for the formation and dimerization of proteasome precursor complexes containing beta subunits. Dimerization coincides with the incorporation of the last beta subunit (beta7). Additional modules important for the assembly of precursor complexes and their dimerization reside in the beta subunits themselves, either as transient or as permanent extensions. Particularly important domains are the propeptide of beta5 and the C-terminal extensions of beta2 and beta7. Upon maturation of the active sites by autocatalytic processing, UMP1 is degraded by the native proteasome.
26S 蛋白酶体是真核细胞细胞质和核中的一种非溶酶体蛋白酶。它的主要功能是介导泛素依赖性蛋白水解。26S 蛋白酶体是一个由 20S 蛋白酶体 CP（核心颗粒）和 19S RPs（调节颗粒）组成的多聚体复合物。虽然 26S 蛋白酶体的原子结构尚未确定，但已可获得其 CP 的高分辨率结构。对蛋白酶体复杂组装途径的研究表明，它涉及数量空前的专用伴侣蛋白。CP 的组装本身就涉及三个保守的蛋白酶体组装伴侣蛋白 [PAC1-PAC2、PAC3-PAC4 和 UMP1（泛素介导的蛋白水解 1）]。虽然两个异源二聚体 PAC 被认为参与了七个不同的α亚基环的形成，但 UMP1 对于包含β亚基的蛋白酶体前体复合物的形成和二聚化很重要。二聚化与最后一个β亚基（β7）的掺入同时发生。对于前体复合物的组装及其二聚化的重要附加模块位于β亚基本身中，要么是暂时的，要么是永久性的扩展。特别重要的结构域是β5 的前肽和β2 和β7 的 C 末端延伸。在活性位点通过自动催化加工成熟后，UMP1 被天然蛋白酶体降解。
