PXD066303 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism |
| Description | BCL-xL promotes cell survival by binding BH3-only initiators through its hydrophobic groove. Combining resonance energy transfer assays and molecular dynamics simulations, we unravel that membrane anchoring of BCL-xL via its C-terminal tail selectively advantages binding to membrane-anchored PUMA initiator over BH3 mimetic ligands of the groove. This is due to the combined allosteric effect on BH3-in-groove binding of BCL-xL and PUMA tail anchors. Moreover, doubly anchored PUMA / BCL-xL complexes recruit endogenous BAX, which favors their antagonism by BH3 mimetics. BAX’s C-terminal sequence alone is suffi-cient to enhance BH3 mimetics induced death in cells expressing PUMA / BCL-xL. Our work supports a model in which the survival function of BCL-xL is regulated by a complex inter-play between its tail anchor and those of its interacting partners. This enables both resistance to pharmacological inhibitors and modulation by BAX, which functions as a crucial feedback disruptor of the BCL-xL network. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-12-08 |
| AnnouncementXML | Submission_2025-12-07_17:29:44.624.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | François Guillonneau |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | methylthiolated residue; monohydroxylated residue |
| Instrument | TripleTOF 5600 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-07-18 02:17:51 | ID requested | |
| ⏵ 1 | 2025-12-07 17:29:45 | announced | |
Publication List
| 10.1038/s41467-025-65509-1; |
| Maillet L, F, é, tiveau A, Lalier L, Martin N, Barill, é, -Nion S, Guette C, Gautier F, T, é, letch, é, a S, Juin PP, Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism. Nat Commun, 16(1):10621(2025) [pubmed] |
Keyword List
| submitter keyword: PUMA, Tail anchors, BCL-xL, BAX, TripleTOF 5600+, BH3 mimetic,SWATH |
Contact List
| Laurent Maillet |
|---|
| contact affiliation | Nantes Université, INSERM, CNRS, CRCI2NA, U1307, UMR6075, F-44000 Nantes, France. |
| contact email | laurent.maillet@inserm.fr |
| lab head | |
| François Guillonneau |
|---|
| contact affiliation | Institut de Cancerologie de l'Ouest (ICO) Angers |
| contact email | francois.guillonneau@inserm.fr |
| dataset submitter | |
Full Dataset Link List
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/2025/12/PXD066303 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD066303
- Label: PRIDE project
- Name: Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism
