Within the isolated lid sub-complex of the proteasome, a finely tuned network of interactions maintains the deubiquitinase in an inhibited conformation; dramatic rearrangements of the lid subunits upon incorporation into the holoenzyme lead to the deubiquitinase’s activation.
Inducing presomitic mesoderm (PSM)-fated ES cells clarified that Ripply2 directly interacts with Tbx6 and degrades Tbx6 in proteasome-ubiquitin pathway by recruiting the 26S proteasome, which is a PSM-specific event to define the segment border during mouse somitogenesis.
One α-synuclein strain inhibited proteasome activity and induced apparent pathologies, while the other did not, indicating a strain-dependent toxicity of α-synuclein aggregates, which support a prion-like behavior of α-synuclein.
The 26S proteasome lid subcomplex acts as an external scaffold whose interactions with the ATPase motor stabilize the substrate-engagement-competent state, and control conformational changes upon engagement for subsequent degradation steps.
Structures of active and inactive conformations of a PP2C family phosphatase reveal a conserved switch that controls enzymatic activity and point to an unexpected relationship between phosphatases and proteasomal proteases.