Assembly chaperone Nas6 selectively destabilizes 26S proteasomes with defective regulatory particle-core particle interfaces

Controlled atmosphere storage drive proteomic change in Chinese Daohuaxiang

“…In this study, 26S proteasome regulatory particle triple-A ATPase subunit 6 (OsRPT6) had a significant impact on the differential protein expression between 35 % CO 2 -CA storage and the control. The 26S proteasome is the main molecular machine responsible for protein degradation in eukaryotic cells ( Jennifer, Warnock, Jobin, & Robert, 2023 ), which participates in almost all biological activities of organisms by selectively degrading target proteins ( Jennifer et al, 2023 ). Ubiquitin-mediated protein degradation requires a lot of energy consumption, and therefore the degradation of protein were reduced during 35 % CO 2 -CA storage.…”

Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis

“…In a similar vein to the role of assembly chaperones in suppressing ATPase activity of the free base subcomplex, Nas6 was recently shown to be unique among the chaperones in that it can destabilize proteasomes with defects at the RP–CP interface [ 100 ]. Typically, the RP docks onto the CP on one or both ends in part through highly conserved, flexible C-termini tail regions of specific ATPase subunits [ 67 ].…”

“…Disruptions to the HbYX-α pocket interactions on either side of the RP–CP interface yielded a Nas6-dependent reduction in the levels of mature proteasomes and a corresponding increase in the levels of free RP and CP, consistent with a destabilization of this interface [ 100 ]. Importantly, this destabilization could be completely rescued via deletion of NAS6 , indicating it was not simply due to a substantial weakening of the RP–CP interface.…”

“…It is likely that any defects at the RP–CP interface will weaken the interaction between these complexes; this in principle will enhance the frequency that they dissociate, providing Nas6 opportunities to bind and sequester defective RPs. However, Nas6 accumulated on RPs even when RP–CP interface defects were present on the CP rather than the RP, and deletion of NAS6 in cells harboring RP–CP defects suppressed the accumulation of free RP and CP, suggesting this former possibility is unlikely [ 100 ]. Instead, disruptions to the RP–CP interface may open enough space between these two subcomplexes for Nas6 to bind and sterically interfere with their stable interaction in one or more conformations associated with the ATPase cycle.…”