9HEU
Co-chaperone Bag1-bound human 26S proteasome in SBAG1 state
This is a non-PDB format compatible entry.
Summary for 9HEU
| Entry DOI | 10.2210/pdb9heu/pdb |
| EMDB information | 52097 |
| Descriptor | Proteasome subunit alpha type-6, 26S protease regulatory subunit 6B, 26S proteasome regulatory subunit 10B, ... (35 entities in total) |
| Functional Keywords | protein degradation, protease, aaa+ atpase, hsp70, cochaperone, bag1, complex, ubiquitin, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 47 |
| Total formula weight | 1693876.51 |
| Authors | Cheng, T.C.,Sakata, E.,Muntaner, J.,Maestro-Lopez, M.,Cuellar, J.,Valpuesta, J.M. (deposition date: 2024-11-14, release date: 2025-12-31, Last modification date: 2026-03-04) |
| Primary citation | Maestro-Lopez, M.,Cheng, T.C.,Muntaner, J.,Menendez, M.,Alonso, M.,Schweitzer, A.,Ishizaka, M.,Tomko Jr., R.J.,Cuellar, J.,Valpuesta, J.M.,Sakata, E. Structures of the 26 S proteasome in complex with the Hsp70 co-chaperone Bag1 reveal a mechanism for direct substrate transfer. Sci Adv, 12:eadz3026-eadz3026, 2026 Cited by PubMed Abstract: Coupling between the chaperone and degradation systems, particularly under stress, is essential for eliminating unfolded proteins. The co-chaperone Bag1 links Hsp70 to the 26 proteasome, recruiting Hsp70-bound clients for proteasomal degradation. Here, we present cryo-electron microscopy structures of the Bag1-bound 26 proteasome, revealing unprecedented conformational rearrangements within the 19 regulatory particle. Bag1 binding to the Rpn1 induces a marked reconfiguration of AAA adenosine triphosphatase (ATPase) ring, disrupting its canonical spiral staircase and remodeling the central channel architecture. This reconfiguration generates a large cavity above the substrate entry gate of the 20 core particle. The conserved pore-2 loops of ATPases Rpt2 and Rpt5 play critical roles in opening of the 20 gate, enabling substrate entry into proteolytic chamber independently of ubiquitination. These findings suggest a previously unknown mechanism of the proteasomal degradation, by which remodeling the central cavity and 20 gate in the presence of Bag1, possibly bypassing the need for ubiquitination. PubMed: 41719407DOI: 10.1126/sciadv.adz3026 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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