PXD063358 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5 |
| Description | Adaptor proteins often serve as hubs to regulate diverse protein complexes in cells. This multitude of functions can complicate the study of adaptors, as their genetic disruption typically impairs the activities of all parent complexes (or ‘complexoforms’). Here we describe the chemical proteomic analysis of bicyclopyrrolidine acrylamide stereoprobes in human cells, leading to the discovery of a ligand – FWG-33B – that stereoselectively reacts with cysteine-100 (C100) of the methyltransferase (MT) adaptor TRMT112. FWG-33B showed negligible reactivity with uncomplexed recombinant TRMT112, and this interaction was restored exclusively in the presence of METTL5, but not other MT partners of TRMT112. A co-crystal structure revealed that FWG-33B binds at a composite pocket proximal to C100 that is templated by METTL5 and absent in other TRMT112:MT complexes. Subtle structural rearrangements promoted by FWG-33B in turn lead to allosteric agonism of METTL5, thus revealing how covalent ligands targeting a pleiotropic adaptor can confer partner-specific functional effects through reactivity with a single complexoform. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-01-08 |
| AnnouncementXML | Submission_2026-01-08_06:19:30.890.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Friedrich Wieland Goetzke |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | iodoacetamide derivatized residue |
| Instrument | Orbitrap Eclipse; Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-04-26 17:10:07 | ID requested | |
| ⏵ 1 | 2026-01-08 06:19:31 | announced | |
Publication List
Keyword List
Contact List
| Benjamin Cravatt |
|---|
| contact affiliation | Scripps Research, US |
| contact email | cravatt@scripps.edu |
| lab head | |
| Friedrich Wieland Goetzke |
|---|
| contact affiliation | Scripps Research |
| contact email | fgoetzke@scripps.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD063358
- Label: PRIDE project
- Name: Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5
