摘要：SummaryProteasomes are multi-subunit protease complexes found in all domains of life. The maturation of the core particle (CP), which harbors the active sites, involves dimerization of two half CPs (HPs) and an autocatalytic cleavage that removes β propeptides. How these steps are regulated remains poorly understood. Here, we used theRhodococcus erythropolisCP to dissect this processin vitro. Our data show that propeptides regulate the dimerization of HPs through flexible loops we identified. Furthermore, N-terminal truncations of the propeptides accelerated HP dimerization and decelerated CP auto-activation. We identified cooperativity in autocatalysis and found that the propeptide can be partially cleaved by adjacent active sites, potentially aiding an otherwise strictly autocatalytic mechanism. We propose that cross-processing during bacterial CP maturation is the underlying mechanism leading to the observed cooperativity of activation. Our work suggests that the bacterial β propeptide plays an unexpected and complex role in regulating dimerization and autocatalytic activation.Graphical AbstractDisplay OmittedHighlights•A flexible region in β propeptide regulates proteasome core particle (CP) formation•Identified pre-holocomplex distinguishes dimerization from autocatalytic activation•Cooperativity found in proteasome core particle (CP) activation•Bacterial CP displayed propeptide cross-cleavageBiological Sciences; Biochemistry; Microbiology
