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- Title
Integration of the catalytic subunit activates deneddylase activity in vivo as final step in fungal COP9 signalosome assembly.
- Authors
Beckmann, Elena A.; Köhler, Anna M.; Meister, Cindy; Christmann, Martin; Draht, Oliver W.; Rakebrandt, Nikolas; Valerius, Oliver; Braus, Gerhard H.
- Abstract
The eight-subunit COP9 signalosome ( CSN) is conserved from filamentous fungi to humans and functions at the interface between cellular signalling and protein half-life control. CSN consists of six PCI and two MPN domain proteins and forms a scaffold for additional interacting proteins. CSN controls protein stability in the ubiquitin-proteasome system where the MPN domain CSN5/ CsnE subunit inactivates cullin- RING ligases. The CSN5/ CsnE isopeptidase functions as deneddylase and removes the ubiquitin-like protein Nedd8. The six PCI domain proteins of human CSN form a horseshoe-like ring and all eight subunits are connected by a bundle of C-terminal α-helices. We show that single deletions of any csn subunit of A spergillus nidulans resulted in the lack of deneddylase activity and identical defects in the coordination of development and secondary metabolism. The CSN1/ CsnA N-terminus is dispensable for deneddylase activity but required for asexual spore formation. Complex analyses in mutant strains revealed the presence of a seven-subunit pre- CSN without catalytic activity. Reconstitution experiments with crude extracts of deletion strains and recombinant proteins allowed the integration of CSN5/ CsnE into pre- CSN resulting in an active deneddylase. This supports a stable seven subunit pre- CSN intermediate where deneddylase activation in vivo can be controlled by CSN5/ CsnE integration as final assembly step.
- Subjects
SCAFFOLD proteins; CELLULAR signal transduction; FILAMENTOUS fungi; CATALYTIC activity; PROTEASOMES; SECONDARY metabolism; PROTEIN stability
- Publication
Molecular Microbiology, 2015, Vol 97, Issue 1, p110
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/mmi.13017