title: Order of the proteasomal ATPases and eukaryotic proteasome assembly.
abstract: The 26S proteasome is responsible for a large fraction of the regulated protein degradation in eukaryotic cells. The enzyme complex is composed of a 20S proteolytic core particle (CP) capped on one or both ends with a 19S regulatory particle (RP). The RP recognizes and unfolds substrates and translocates them into the CP. The RP can be further divided into lid and base subcomplexes. The base contains a ring of six AAA+ ATPases (Rpts) that directly abuts the CP and is responsible for unfolding substrates and driving them into the CP for proteolysis. Although 120 arrangements of the six different ATPases within the ring are possible in principle, they array themselves in one specific order. The high sequence and structural similarity between the Rpt subunits presents special challenges for their ordered association and incorporation into the assembling proteasome. In this review, we discuss recent advances in our understanding of proteasomal RP base biogenesis, with emphasis on potential specificity determinants in ring arrangement, and the implications of the ATPase ring arrangement for proteasome assembly.
authors: Department of Molecular Biophysics & Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114, USA.
authors: Robert J
authors: RJ
authors: Tomko
authors: Mark
authors: M
authors: Hochstrasser
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D005057:Eukaryotic Cells / Q000201:enzymology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases