PXD030849 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain |
Description | RING-Between-RING (RBR) E3 ligases mediate ubiquitin transfer through an obligate E3- ubiquitin thioester intermediately prior to substrate ubiquitination. While RBRs share a conserved catalytic module, substrate recruitment mechanisms remain enigmatic and the relevant domains have yet to be identified for any member of the class. Here we characterize the interaction between the auto-inhibited RBR, HHARI (AriH1), and its target protein, 4EHP, using a combination of XL-MS, HDX-MS, NMR, and biochemical studies. The results show that 1) a di-aromatic surface on the catalytic HHARI Rcat domain forms a binding platform for substrates and 2) a phospho-mimetic mutation on the auto-inhibitory Ariadne domain of HHARI promotes release and reorientation of Rcat for transthiolation and substrate modification. The findings represent the first identification of a direct binding interaction between a RING-Between-RING ligase and its substrate. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:48:16.550.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alex Zelter |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-09 11:45:29 | ID requested | |
1 | 2023-05-24 10:58:25 | announced | |
⏵ 2 | 2023-11-14 08:48:17 | announced | 2023-11-14: Updated project metadata. |
Publication List
Reiter KH, Zelter A, Janowska MK, Riffle M, Shulman N, MacLean BX, Tamura K, Chambers MC, MacCoss MJ, Davis TN, Guttman M, Brzovic PS, Klevit RE, Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain. Structure, 30(9):1269-1284.e6(2022) [pubmed] |
Keyword List
submitter keyword: Kojak,Cross-linking Mass Spectrometry, ProXL, Skyline, Cullin, XL-MS, HHARI, ubiquitin, RBR, E3 ligase |
Contact List
Rachel E. Klevit |
contact affiliation | Department of Biochemistry, University of Washington, Seattle, WA, USA |
contact email | klevit@uw.edu |
lab head | |
Alex Zelter |
contact affiliation | Department of Biochemistry, University of Washington, Seattle |
contact email | azelter@uw.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030849
- Label: PRIDE project
- Name: Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain