Fungal COP9 signalosome assembly requires connection of two trimeric intermediates for integration of intrinsic deneddylase

The conserved eight-subunit COP9 signalosome (CSN) is required for multicellular fungal development. The CSN deneddylase cooperates with the Cand1 exchange factor to control replacements of E3 ubiquitin cullin RING ligase receptors, providing specificity to eukaryotic protein degradation. Aspergillu...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2023-08, Vol.120 (35), p.1-e2305049120
Main Authors: Bakti, Fruzsina, Stupperich, Helena, Schmitt, Kerstin, Valerius, Oliver, Köhler, Anna M., Meister, Cindy, Strohdiek, Anja, Harting, Rebekka, Sasse, Christoph, Heimel, Kai, Neumann, Piotr, Ficner, Ralf, Braus, Gerhard H.
Format: Article
Language:English
Subjects:
Assembly
Biodegradation
Biological Sciences
Cullin
Fungi
Integration
Intermediates
Localization
Mass spectrometry
Mass spectroscopy
Ubiquitin
Ubiquitin-protein ligase
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Summary:The conserved eight-subunit COP9 signalosome (CSN) is required for multicellular fungal development. The CSN deneddylase cooperates with the Cand1 exchange factor to control replacements of E3 ubiquitin cullin RING ligase receptors, providing specificity to eukaryotic protein degradation. Aspergillus nidulans CSN assembles through a heptameric pre-CSN, which is activated by integration of the catalytic CsnE deneddylase. Combined genetic and biochemical approaches provided the assembly choreography within a eukaryotic cell for native fungal CSN. Interactomes of functional GFP-Csn subunit fusions in pre-CSN deficient fungal strains were compared by affinity purifications and mass spectrometry. Two distinct heterotrimeric CSN subcomplexes were identified as pre-CSN assembly intermediates. CsnA-C-H and CsnD-F-G form independently of CsnB, which connects the heterotrimers to a heptamer and enables subsequent integration of CsnE to form the enzymatically active CSN complex. Surveillance mechanisms control accurate Csn subunit amounts and correct cellular localization for sequential assembly since deprivation of Csn subunits changes the abundance and location of remaining Csn subunits.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2305049120