PXD049315

PXD049315 is an original dataset announced via ProteomeXchange.

Title	Inhibition of Oligomeric BAX by an Anti-Apoptotic Dimer
Description	BAX is a pro-apoptotic BCL-2 protein that resides in the cytosol as a monomer until triggered by cellular stress to transform into an oligomer that permeabilizes the mitochondria and induces apoptosis. We previously reported the generation of a full-length BAX oligomer (BAXO) that recapitulates pro-apoptotic functionality. Here, we find that full-length BCL-w can be induced to form a symmetric dimer (BCL-wD) that dissociates BAXO, inhibits its mitochondrial translocation, induces its retrotranslocation, and thereby blocks its membrane-porating activity. Structure-function analyses revealed discrete conformational changes upon BCL-w dimerization and reciprocal structural impacts upon BCL-wD and BAXO interaction. SAXS analysis demonstrated that BAXO forms pores by inducing negative Gaussian membrane curvature, which is reversed by positive Gaussian curvature exerted by BCL-wD. Our studies reveal an additional mechanism of apoptotic regulation mediated by the protein and membrane interactions of higher-order BCL-2 family multimers, redefining the “point of no return” for BAX-mediated apoptosis.
HostingRepository	PRIDE
AnnounceDate	2025-11-21
AnnouncementXML	Submission_2025-11-21_14:32:00.644.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Wales
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-10 10:32:03	ID requested
⏵ 1	2025-11-21 14:32:01	announced

10.1016/J.CELL.2025.10.037;

submitter keyword: BCL-w

BAX

BCL-w dimer

BAX oligomer

HDX-MS

hydrogen/deuterium exchange mass spectrometry

apoptotic regulation

Thomas E. Wales
contact affiliation	Northeastern University
contact email	t.wales@northeastern.edu
lab head
Thomas Wales
contact affiliation	Northeastern University
contact email	t.wales@northeastern.edu
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/2025/11/PXD049315

PRIDE project URI

• PRIDE
  1. PXD049315
     1. Label: PRIDE project
     2. Name: Inhibition of Oligomeric BAX by an Anti-Apoptotic Dimer