title: Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly.
abstract: To understand the role of the pro-peptide in proteasome assembly, we have determined structures of the Rhodococcus proteasome and a mutant form that prevents the autocatalytic removal of its pro-peptides. The structures reveal that the pro-peptide acts as an assembly-promoting factor by linking its own beta-subunit to two adjacent alpha-subunits, thereby providing a molecular explanation for the observed kinetics of proteasome assembly. The Rhodococcus proteasome has been found to have a substantially smaller contact region between alpha-subunits compared to those regions in the proteasomes of Thermoplasma, yeast, and mammalian cells, suggesting that a smaller contact area between alpha-subunits is likely the structural basis for the Rhodococcus alpha-subunits not assembling into alpha-rings when expressed alone. Analysis of all available beta-subunit structures shows that the contact area between beta-subunits within a beta-ring is not sufficient for beta-ring self-assembly without the additional contact provided by the alpha-ring. This appears to be a fail-safe mechanism ensuring that the active sites on the beta-subunits are activated only after proteasome assembly is complete.
authors.affiliation: Graduate Group in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: István
authors.initials: I
authors.lastname: Nagy
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumeister
authors.forename: Bing K
authors.initials: BK
authors.lastname: Jap
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry*; D004789:Enzyme Activation / Q000235:genetics; D004792:Enzyme Precursors / Q000737:chemistry; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000737:chemistry*; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D012240:Rhodococcus / Q000201:enzymology*
chemical_list: D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D021122:Protein Subunits; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex