THE HUMAN PROTEASOMAL SUBUNIT HSC8 INDUCES RING FORMATION OF OTHER ALPHA-TYPE SUBUNITS

The eukaryotic 20 S proteasome is a barrel-shaped protease complex, ma de up of four seven-membered rings. The outer and inner rings contain seven different alpha and beta-type subunits, respectively, each subun it located at a defined position. Recently, we have reported that the recombinant human alpha-type subunit C8 (HsC8) assembles into a heptam eric ring-like structure by itself. In the present study we show that the two naturally neighboring alpha-type subunits of HsC8, HsPROS30 an d HsPROS27, do not form ring-like complexes by themselves, but only di mers. This indicates that the propensity to form homo-oligomeric rings is not a general feature among human alpha-type subunits. However, co expression of HsC8 and either of these neighbor alpha-type subunits re sults in the formation of hetero-oligomeric ring complexes, resembling the HsC8 ring-like structure. The ratio between the two types of subu nits in the mixed complexes is surprisingly heterogeneous, varying fro m very high to very low HsC8 content. The three tested alpha-type subu nits thus apparently lack binding sites that selectively interact with a specific neighboring subunit. This suggests that the correct positi oning of the different alpha-type subunits in the eukaryotic 20 S prot easome is not dictated by the alpha-type subunits themselves, but rath er by the interaction with specific beta-type subunits. (C) 1998 Acade mic Press Limited.