Molecular dissection of the 11S REG (PA28) proteasome activators.
The proteasome activators known as 11S REG or PA28 were discovered about 10 years ago. They are homo- or heteroheptameric rings that bind to the ends of 20S proteasomes and activate cleavage of peptides but not folded proteins. In this article, we focus on structural features of three homologous REG subunits (termed alpha, beta, gamma) that contribute to their oligomerization, proteasome binding and proteasome activation. We review a number of published studies on the biochemical properties of REGs and present new results in which N-terminal sequences and sequences flanking REG activation loops have been exchanged between homologs. Characterization of these chimeras and previously constructed C-terminal chimeras reveal that N-terminal and loop flanking sequences affect oligomerization, whereas C-terminal sequences are essential for proteasome binding. None of these regions is responsible for the broad activation specificity of REGs alpha/beta versus the narrow specificity of REGgamma. Rather, mutation in a single residue lining the channel through the REGgamma heptamer changes the activation property of the gamma homolog to match that of REGs alpha and beta.
Li
J
J
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City 84132-0001, USA.
Rechsteiner
M
M
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D020536:Enzyme Activators / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment / Q000145:classification
D020536:Enzyme Activators; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C085047:PSME1 protein, human; D011506:Proteins; D011993:Recombinant Fusion Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex