Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover - PubMed
6 hours ago
- #proteasome
- #ubiquitin-independent degradation
- #cryo-electron microscopy
- Midnolin mediates ubiquitin-independent degradation of nuclear proteins via the 26S proteasome.
- Nine cryo-EM structures show midnolin binds proteasome's RPN1 via C-terminal helix and positions substrate-binding Catch domain above entry.
- Midnolin's ubiquitin-like domain interacts non-catalytically with RPN11, facilitating substrate translocation.
- Four spiral staircase conformations of AAA+ ATPase hexamer observed during substrate translocation cycle.
- Findings provide mechanistic insights and potential strategies for targeting nuclear proteins directly.