The substrate translocation channel of the proteasome

The core particle (CP) of the yeast proteasome is composed of four heptamer ic rings of subunits arranged in a hollow, barrel-like structure. We have f ound that the CP is autoinhibited by the N-terminal tails of the outer (alp ha) ring subunits. Crystallographic analysis showed that deletion of the ta il of the alpha3 subunit opens a channel into the proteolytically active in terior chamber of the CP, thus derepressing peptide hydrolysis. In the late nt state of the particle, the tails prevent substrate entry by imposing top ological closure on the CP. Inhibition by the alpha subunit tails is reliev ed upon binding of the regulatory particle to the CP to form the proteasome holoenzyme. Opening of the CP channel by assembly of the holoenzyme is reg ulated by the ATPase domain of Rpt2, one of 17 subunits in the RP. Thus, op en-channel mutations in CP subunits suppress the closed-channel phenotype o f an rpt2 mutant. These results identify a specific mechanism for allosteri c regulation of the CP by the RP. (C) 2001 Societe francaise de biochimie e t biologie moleculaire / Editions scientifiques et medicales Elsevier SAS. All rights reserved.