PXD047229

PXD047229 is an original dataset announced via ProteomeXchange.

Title	Noncanonical assembly, neddylation, and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex
Description	Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, "cullin-RING" and "RBR", are individually found in several hundred E3 ligases in humans, 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 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 amongst RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrate ubiquitylation relies on both CUL9's neddylated cullin and RBR domains achieving self-assembled and chimeric cullin-RING/RBR E3 ligase activity.
HostingRepository	PRIDE
AnnounceDate	2024-04-09
AnnouncementXML	Submission_2024-04-09_07:43:07.217.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-24 15:28:13	ID requested
⏵ 1	2024-04-09 07:43:07	announced

10.1038/S41594-024-01257-Y;

submitter keyword: Ubiquitin, RBX1, TP53, APEX2, NEDD8, RBR, cullin, CUL9, E3-ligase

Brenda A. Schulman
contact affiliation	Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany
contact email	schulman@biochem.mpg.de
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/04/PXD047229

PRIDE project URI

• PRIDE
  1. PXD047229
     1. Label: PRIDE project
     2. Name: Noncanonical assembly, neddylation, and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex