8YIZ

Cryo-EM structure of human proteasome assembly intermediate preholo-2

Summary for 8YIZ

• Entry DOI: 10.2210/pdb8yiz/pdb
• EMDB information: 39334
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome subunit beta type-5, ... (16 entities in total)
• Functional Keywords: protein degradation, proteasome, 20s proteasome, assembly, assembly chapreone, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 30
• Total formula weight: 821329.34

Authors

Han, Y.,Han, Q.,Tang, Q.,Zhang, Y.,Liu, K. (deposition date: 2024-02-29, release date: 2025-01-15, Last modification date: 2025-01-22)

Primary citation

Han, Y.,Han, Q.,Tang, Q.,Zhang, Y.,Liu, K.
Molecular basis for the stepwise and faithful maturation of the 20 S proteasome.
Sci Adv, 11:eadr7943-eadr7943, 2025

PubMed Abstract: The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20 proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive. Here, we captured endogenous maturation intermediates of human 20 proteasome, which are low abundance and highly dynamic, and determined their structures by cryo-electron microscopy. Through structure-based functional studies, we identified the key switches that remodel and activate the proteolytic sites. Our results also revealed that the POMP degradation is tightly controlled by a dual-checking mechanism, while the α5 subunit senses POMP degradation to induce PAC1/2 release, achieving the full maturation. These findings elucidate mechanisms directing and safeguarding the proteasome maturation and set basis for building proteasomes to counteract the decline of protein degradation in aging and disease.

PubMed: 39792683
DOI: 10.1126/sciadv.adr7943

Experimental method

ELECTRON MICROSCOPY (3.79 Å)