STRUCTURAL AND FUNCTIONAL-PROPERTIES OF PROTEASOME ACTIVATOR PA28

The proteasome activator PA28 or 11S regulator is a protein complex co mposed of two different but homologous polypeptides, termed PA28 alpha and PA28 beta. The purified activator protein (similar to 200 kDa) is a ring-shaped heteromultimer containing the two polypeptides, possibl y with an (alpha(3) beta(3) stoichiometry. The activator, which by its elf shows no hydrolytic activity elicits activation of the proteasome' s multiple peptidase activities by binding to the terminal rings of th e proteinase. In vitro, active PA28 can be reconstituted from isolated alpha and beta subunits, yielding two different oligomers: with the s ingle alpha subunit, PA28 alpha homomultimers with moderate stimulator y activity toward 20S proteasomes are obtained whereas isolated beta-s ubunits are unable to form oligomers and are devoid of stimulatory act ivity. However, in the presence of both subunits, alpha beta heteromul timers form, concomitant with restoration of full stimulatory activity . The recent finding that PA28 modulates the proteasome-catalyzed prod uction of antigenic peptides presented to the immune system on MHC cla ss I molecules indicates a cellular function of the activator in antig en processing.