Experimental and computational analyses reveal how proteasomal hydrolysis is regulated and show that peptide transport is the rate-limiting step and the main differentiating factor between human standard- and immuno-proteasomes.
The proteasomal deubiquitinase UCHL5/UCH37 uses a face distinct from the canonical ubiquitin binding site to engage K48-linked ubiquitin chains and catalyze chain debranching.
Corey M Dambacher, Evan J Worden ... Gabriel C Lander
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.
Senthil K Radhakrishnan, Willem den Besten, Raymond J Deshaies
The enzyme p97/VCP regulates the activity of the transcription factor Nrf1 to promote increased transcription of genes that encode proteasome subunits following inhibition of the proteasome.
Empirical energy landscape allows simulating the structural dynamics of the proteasomal ATPase complex, which yields predictions that are widely consistent with experimental observations and reveals the functional mechanism of the proteasome in substrate degradation.
Through interactions with both ubiquitin units that emanate from a branch point in polyubiquitin, UCH37 recognizes and hydrolyzes branched chains to promote proteasome-mediated degradation upon proteolytic stresses.
Proteasomes are protected from autophagic elimination upon carbon starvation by sequestration into cytoplasmic storage granules, which aid cell fitness by providing a cache of proteasomes that can be rapidly remobilized when carbon availability improves.
Peter Tsvetkov, Marc L Mendillo ... Susan Lindquist
Reducing the expression of 19S subunits shifts the ratio of 20S/26S proteasome complexes and provides a powerful survival advantage in the face of lethal proteasome inhibition.