Fig. 8: Model of critical residues and induced conformational changes involved in the molecular mechanism of gate-opening induced by a minimal HbYX motif.

a Summary figure of HbYX motif interactions with intersubunit pocket. Color key shows residues that were mutated in this study and summarizes their effects on ZYA function. b Schematic demonstrating the function of the IT switch (I12, T13) that stabilizes the open and closed states of the proteasome gate. Functionally the IT switch is allosterically tethered to the Pro17 position, which is affected by the binding of ZYA and likely all proteasome activators that induce gate-opening. A color key shows residues that were mutated in this study on the IT switch and summarizes their effects on the function of the gating in the T20S proteasome.