PXD042481

PXD042481 is an original dataset announced via ProteomeXchange.

Title	Folding correctors can retore CFTR post-translational folding landscape by allosteric domain-domain coupling
Description	Numerous missense mutations cause misfolding and premature degradation of ATP-binding cassette (ABC)-transporters-transporters, accounting for several human conformational diseases with poorly under-stood molecular mechanisms. Recent breakthroughs in small molecule combination therapy led transformative improvement of patients’ outlook in cystic fibrosis (CF), caused by several mutations, including the most prevalent deletion of the F508 (delF508) in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, a member of the large ABC-transporter superfamily. By relying on hydrogen deuterium exchange mass spectrometry (HDX-MS), molecular dynamic simulations and biochemical techniques, we demonstrate that the recently approved pharmacophores (VX-445 [elexacaftor] and/or VX-809 [lumacaftor]) mechanism of action relies on a complex network of dynamic inter-domain allosteric interactions to restore the post-translational coupled domain folding and the final fold stability of mutant CFTRs.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_09:24:21.243.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Naoto Soya
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Eclipse; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-24 11:58:18	ID requested
⏵ 1	2024-01-26 09:24:22	announced

Soya N, Xu H, Roldan A, Yang Z, Ye H, Jiang F, Premchandar A, Veit G, Cole SPC, Kappes J, Heged, ü, s T, Lukacs GL, Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling. Nat Commun, 14(1):6868(2023) [pubmed]

10.1038/s41467-023-42586-8;

submitter keyword: biogenesis, post-translational protein folding, cystic fibrosis mutation, protein dynamics, coupled domain folding,Hydrogen-deuterium exchange and mass spectrometry (HDX-MS), ABC-transporter, folding corrector drugs, allostery, cystic fibrosis transmembrane conductance regulator (CFTR)

Gergely L. Lukacs
contact affiliation	McGill University, department of physiology, Canada
contact email	gergely.lukacs@mcgill.ca
lab head
Naoto Soya
contact affiliation	McGill University
contact email	naoto.soya@mcgill.ca
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/2024/01/PXD042481

PRIDE project URI

• PRIDE
  1. PXD042481
     1. Label: PRIDE project
     2. Name: Folding correctors can retore CFTR post-translational folding landscape by allosteric domain-domain coupling