PXD043646 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Cryo-EM visualizes substrate channeling and E2 multisite phosphorylation configuring ubiquitin ligation by GID/CTLH E3 |
Description | Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryo-EM, biochemistry, and cell biology reveal exquisitely specific GID/CTLH-Ubc8/UBE2H pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 Å away, mediated by E2 phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C-termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data illustrate phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, immobilizes the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites. |
HostingRepository | PRIDE |
AnnounceDate | 2023-12-18 |
AnnouncementXML | Submission_2023-12-18_09:03:44.807.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mario Oroshi |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-10 08:47:45 | ID requested | |
⏵ 1 | 2023-12-18 09:03:45 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Proteomics |
Contact List
Matthias Mann |
contact affiliation | Research Department "Proteomics and Signal Transduction" |
contact email | mmann@biochem.mpg.de |
lab head | |
Mario Oroshi |
contact affiliation | Proteomics |
contact email | oroshi@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043646
- Label: PRIDE project
- Name: Cryo-EM visualizes substrate channeling and E2 multisite phosphorylation configuring ubiquitin ligation by GID/CTLH E3