PXD024479

PXD024479 is an original dataset announced via ProteomeXchange.

Title	The Conformational Stability of Pro-apoptotic BAX is Dictated by Discrete Residues of the Protein Core
Description	BAX is a pro-apoptotic member of the BCL-2 family, which regulates the balance between cellular life and death. During homeostasis, BAX predominantly resides in the cytosol as a latent monomer but, in response to stress, transforms into an oligomeric protein that permeabilizes the mitochondria, leading to cell death. Because renegade BAX activation poses a grave risk to the cell, the architecture of BAX must ensure monomeric stability yet simultaneously enable conformational change upon stress signaling. The specific structural features that afford both stability and dynamic flexibility remain ill-defined and represent a critical control point of BAX regulation. Here, we identified a nexus of interactions involving four discrete residues of the BAX core α5 helix that are individually essential to maintaining the structure and latency of monomeric BAX and are collectively required for dimeric assembly. We compared the HDX MS profile of full-length recombinant wild-type BAX in solution with that of the BAX L113A, F114A, Y115A, and F116A single point mutants. In each case, we observed striking, regiospecific consequences of replacing the bulky hydrophobic residue with alanine. We also compared HDX in a construct of α2-α5 for the wt protein as well as mutants. The dual yet distinct roles of these residues reveals the intricacy of BAX conformational regulation and opportunities for therapeutic modulation.
HostingRepository	PRIDE
AnnounceDate	2021-08-26
AnnouncementXML	Submission_2021-08-26_07:04:03.866.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-02 22:56:13	ID requested
⏵ 1	2021-08-26 07:04:04	announced

Bloch NB, Wales TE, Prew MS, Levy HR, Engen JR, Walensky LD, The conformational stability of pro-apoptotic BAX is dictated by discrete residues of the protein core. Nat Commun, 12(1):4932(2021) [pubmed]

submitter keyword: BAX, apoptosis, Bcl-2 protein, hydrogen deuterium exchange, HDXMS

John R. Engen
contact affiliation	Department of Chemistry & Chemical Biology, Northeastern University
contact email	j.engen@northeastern.edu
lab head
John R. Engen
contact affiliation	Northeastern University
contact email	j.engen@northeastern.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024479
     1. Label: PRIDE project
     2. Name: The Conformational Stability of Pro-apoptotic BAX is Dictated by Discrete Residues of the Protein Core