PXD036945-1

PXD036945 is an original dataset announced via ProteomeXchange.

Title	Resolving chaperone-assisted protein folding on the ribosome at the peptide level
Description	The cellular environment is critical for efficient protein maturation, but how proteins fold during biogenesis remains poorly understood. We used hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to define, at peptide resolution, the cotranslational chaperone-assisted folding pathway of Escherichia coli dihydrofolate reductase. On the ribosome, the nascent polypeptide folds via structured intermediates not populated during refolding from denaturant. Association with the ribosome allows these intermediates to form, as otherwise destabilizing C-terminal sequences remain confined in the ribosome exit tunnel. We find that partially-folded nascent chains recruit the chaperone Trigger factor, which uses a large composite hydrophobic/hydrophilic interface to engage folding intermediates without disrupting their structure. In addition, we comprehensively mapped dynamic interactions between the nascent chain and ribosomal proteins, tracing the path of the emerging polypeptide during synthesis. Our work provides a high-resolution description of de novo protein folding dynamics, thereby revealing new mechanisms by which cellular factors shape the conformational search for the native state.
HostingRepository	PRIDE
AnnounceDate	2024-07-12
AnnouncementXML	Submission_2024-07-12_10:25:25.951.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-22 00:31:00	ID requested
⏵ 1	2024-07-12 10:25:26	announced

10.1038/s41594-024-01355-x;

Wales TE, Pajak A, Roeselov, á A, Shivakumaraswamy S, Howell S, Kj, æ, r S, Hartl FU, Engen JR, Balchin D, Resolving chaperone-assisted protein folding on the ribosome at the peptide level. Nat Struct Mol Biol, 31(12):1888-1897(2024) [pubmed]

submitter keyword: HDXMS

hydrogen deuterium exchange mass spectrometry

protein folding

chaperone

ribosome

trigger factor

DHFR

cotranslational folding

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

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/2024/07/PXD036945

PRIDE project URI

• PRIDE
  1. PXD036945
     1. Label: PRIDE project
     2. Name: Resolving chaperone-assisted protein folding on the ribosome at the peptide level