Chaperone-assisted assembly of the proteasome core particle.
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.
Matias
Ana C
AC
Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany.
Ramos
Paula C
PC
Dohmen
R Jürgen
RJ
D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D046912:Multiprotein Complexes; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D021122:Protein Subunits; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C119011:26S proteasome non-ATPase regulatory subunit 13