English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex

MPS-Authors
/persons/resource/persons260927

Horn-Ghetko,  Daniel
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons277906

Hopf,  Linus V.M.
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;
IMPRS-ML: Martinsried, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons295414

Tripathi-Giesgen,  Ishiata
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons298062

Du,  Jiale
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons213734

Kostrhon,  Sebastian
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons275352

Tung Vu,  D.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;
IMPRS-ML: Martinsried, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons128408

Beier,  Viola
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons263653

Steigenberger,  Barbara
Scientific Service Groups, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons131140

Prabu,  J. Rajan
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons276004

Stier,  Luca
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;
IMPRS-ML: Martinsried, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons298064

Bruss,  Elias M.
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons213292

Schulman,  Brenda A.
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Horn-Ghetko, D., Hopf, L. V., Tripathi-Giesgen, I., Du, J., Kostrhon, S., Tung Vu, D., et al. (2024). Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex. Nature Structural & Molecular Biology. doi:10.1038/s41594-024-01257-y.


Cite as: https://hdl.handle.net/21.11116/0000-000F-3C77-9
Abstract
Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly. Within one dimeric subcomplex, an E2-bound RBR domain is activated by neddylation of its own cullin domain and positioning from the adjacent CUL9-RBX1 in trans. Our data show CUL9 as unique among RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrates are recruited to various upstream domains, while ubiquitylation relies on both CUL9's neddylated cullin and RBR domains achieving self-assembled and chimeric cullin-RING/RBR E3 ligase activity.
Here, using cryo-EM, biochemistry and cell biology, the authors reveal the unique assembly, catalytic mechanism, multimodal substrate recruitment and regulation of the atypical ubiquitin ligase complex CUL9-RBX1.