Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly.
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.
Kwon
Young Do
YD
Graduate Group in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA.
Nagy
István
I
Adams
Paul D
PD
Baumeister
Wolfgang
W
Jap
Bing K
BK
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*
D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D021122:Protein Subunits; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex