Structures of the 26 S proteasome in complex with the Hsp70 co-chaperone Bag1 reveal a mechanism for direct substrate transfer - PubMed
9 hours ago
- #proteasome
- #substrate transfer
- #Hsp70
- Structures of the 26S proteasome in complex with Hsp70 co-chaperone Bag1 reveal a mechanism for direct substrate transfer.
- Bag1 links Hsp70 to the 26S proteasome, recruiting Hsp70-bound clients for proteasomal degradation.
- Cryo-EM structures show Bag1 binding to Rpn1 induces conformational rearrangements in the 19S regulatory particle.
- Bag1 binding reconfigures the AAA+ ATPase ring, disrupting its spiral staircase and remodeling the central channel architecture.
- A large cavity forms above the substrate entry gate of the 20S core particle due to Bag1-induced changes.
- Pore-2 loops of ATPases Rpt2 and Rpt5 are critical for opening the 20S gate, enabling substrate entry independently of ubiquitination.
- The findings suggest a new proteasomal degradation mechanism that may bypass ubiquitination.