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Peer-reviewedCC BYNature communications

Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.

  • Mandeep Kaur1
  • Xiang Chen2
  • Stella Y Lee1
  • Tyler M Weaver1,3
  • Bret D Freudenthal1
  • Kylie J Walters4
  • Jeroen Roelofs5
5 affiliations
  1. 1Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., HLSIC 1077, Kansas City, KS, USA.
  2. 2Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  3. 3Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  4. 4Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. [email protected].
  5. 5Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., HLSIC 1077, Kansas City, KS, USA. [email protected].
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Abstract

The proteasome core particle (CP) can be capped by Blm10/PA200, which promotes ATP-independent degradation of disordered proteins and contributes to attenuating antigenic diversity and impacts immunotherapy upon upregulation. The assembly process that leads to Blm10-CP proteasomes remains unresolved and Blm10 is present not only at mature proteasomes but also bound to assembly intermediates. We identified and solved structures of five CP intermediate complexes by cryo-electron microscopy, two of which include Blm10. We find that CP intermediates interactions with Blm10 and Pba1/Pba2 chaperone complex are mutually exclusive and both leads to mature CP production. We further find no synergy between Pba1/Pba2 and Blm10 for CP assembly. These data suggest a parallel assembly pathway exists for Blm10 proteasomes that does not require sequential activity with Pba1/Pba2. Whereas CP affinity for Pba1/Pba2 is reduced during maturation to promote its release, no such affinity switch occurs for Blm10, further suggesting a parallel Blm10-assembly pathway for production of mature Blm10-bound CPs. Altogether, our findings reveal a functionally distinct CP assembly pathway for the production of mature Blm10-CP proteasomes.

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Cite

BibTeXRIS
BibTeX
@article{kaur2026structure,
  title = {{Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.}},
  author = {Mandeep Kaur and Xiang Chen and Stella Y Lee and Tyler M Weaver and Bret D Freudenthal and Kylie J Walters and Jeroen Roelofs},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77943-w},
  url = {https://europepmc.org/article/MED/42901940},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.
AU  - Mandeep Kaur
AU  - Xiang Chen
AU  - Stella Y Lee
AU  - Tyler M Weaver
AU  - Bret D Freudenthal
AU  - Kylie J Walters
AU  - Jeroen Roelofs
PY  - 2026
DA  - 2026/09/21
JO  - Nature communications
DO  - 10.1038/s41467-026-77943-w
UR  - https://europepmc.org/article/MED/42901940
AB  - The proteasome core particle (CP) can be capped by Blm10/PA200, which promotes ATP-independent degradation of disordered proteins and contributes to attenuating antigenic diversity and impacts immunotherapy upon upregulation. The assembly process that leads to Blm10-CP proteasomes remains unresolved and Blm10 is present not only at mature proteasomes but also bound to assembly intermediates. We identified and solved structures of five CP intermediate complexes by cryo-electron microscopy, two of which include Blm10. We find that CP intermediates interactions with Blm10 and Pba1/Pba2 chaperone complex are mutually exclusive and both leads to mature CP production. We further find no synergy between Pba1/Pba2 and Blm10 for CP assembly. These data suggest a parallel assembly pathway exists for Blm10 proteasomes that does not require sequential activity with Pba1/Pba2. Whereas CP affinity for Pba1/Pba2 is reduced during maturation to promote its release, no such affinity switch occurs for Blm10, further suggesting a parallel Blm10-assembly pathway for production of mature Blm10-bound CPs. Altogether, our findings reveal a functionally distinct CP assembly pathway for the production of mature Blm10-CP proteasomes.
SN  - 2041-1723
ER  -