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Dušan Živković,* ; Bosc-Rosati, A.* ; Dafun, A.S.* ; Mourtada, F.* ; Grygier, P.* ; Yazgili, A.S. ; Jansma, M. ; Rawski, M.* ; Czarna, A.* ; Bohn, S. ; Zak, K.M. ; Mourao, A. ; Reiling, N.* ; Zemke, L.* ; Guo, K.* ; Behr, J.* ; Burlet‐Schiltz, O.* ; Popowicz, G.M. ; Marcoux, J.* ; Meiners, S. ; Bousquet, M.*

PA200 modulates immunoproteasome structure and activity.

Nat. Commun. 17:8175 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The proteasome activator PA200 binds to the catalytic core of both standard proteasome (s20S) and the immunoproteasome (i20S); however, whether PA200 uses the same mechanisms to activate i20S remains unknown. In this work, the cryo-EM structures of singly- and doubly-capped i20S-PA200 complexes, combined with complementary in vitro biochemical assays, show that binding of the first PA200 induces allosteric bending of the i20S and widens the opposite α-ring, promoting higher PA200 occupancy and stronger activation compared to the s20S. PA200 also selectively modulates i20S proteolytic activity by enhancing peptide production and shifting cleavage specificity toward caspase-like activity. In cells and tissues co-expressing PA200, s20S, and i20S, PA200 preferentially associates with the i20S. Moreover, PA200 and i20S catalytic subunits are differentially regulated, with PA200 playing a potential role in regulating the i20S subunits' expression. Overall, these findings suggest that PA200 contributes to the regulation of i20S function and dynamics.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Allosteric Regulation ; Proteasome ; Peptide ; Activator (genetics) ; In Vitro ; Cleavage (geology) ; Proteolysis ; Plasma Protein Binding; Proteasome Activator Pa200; 20s Proteasome; Dynamics; Subtypes
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 17, Issue: 1, Pages: , Article Number: 8175 Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Structural Biology (STB)
Cryo-EM facility (CEMP)
Grants Deutsche Forschungsgemeinschaft (German Research Foundation)
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
Agence Nationale de la Recherche (French National Research Agency)