Structural and functional properties of proteasome activator PA28.
The proteasome activator PA28 or 11S regulator is a protein complex composed of two different but homologous polypeptides, termed PA28alpha and PA28beta. The purified activator protein (approximately 200 kDa) is a ring-shaped heteromultimer containing the two polypeptides, possibly with an (alpha3beta3 stoichiometry. The activator, which by itself shows no hydrolytic activity elicits activation of the proteasome's multiple peptidase activities by binding to the terminal rings of the proteinase. In vitro, active PA28 can be reconstituted from isolated alpha and beta subunits, yielding two different oligomers: with the single alpha subunit, PA28alpha homomultimers with moderate stimulatory activity toward 20S proteasomes are obtained whereas isolated beta-subunits are unable to form oligomers and are devoid of stimulatory activity. However, in the presence of both subunits, alphabeta heteromultimers form, concomitant with restoration of full stimulatory activity. The recent finding that PA28 modulates the proteasome-catalyzed production of antigenic peptides presented to the immune system on MHC class I molecules indicates a cellular function of the activator in antigen processing.
Kuehn
L
L
Diabetes-Forschungsinstitut, Düsseldorf, Germany.
Dahlmann
B
B
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D009097:Multienzyme Complexes; D009124:Muscle Proteins; C085047:PSME1 protein, human; D011506:Proteins; D003546:Cysteine Endopeptidases; C486207:PSME2 protein, human; D046988:Proteasome Endopeptidase Complex