PXD058955-1

PXD058955 is an original dataset announced via ProteomeXchange.

Title	Ypl225w-3xFLAG IP-mass spectrometry
Description	Eukaryotic translation elongation factor 1A (eEF1A) is a highly abundant, multi-domain GTPase. Post-translational steps essential for eEF1A biogenesis are carried out by bespoke chaperones but co-translational mechanisms tailored to eEF1A folding remain unexplored. Here, we find that the N-terminal, GTP-binding domain of eEF1A is prone to co-translational misfolding and using computational approaches, yeast genetics, and microscopy analysis, we identify the conserved yet uncharacterized yeast protein Ypl225w as a chaperone dedicated to solving this problem. Proteomics and biochemical reconstitution reveal that the Ypl225w-ribosomal eEF1A nascent chain interaction depends on additional binding of Ypl225w to the UBA domain of nascent polypeptide-associated complex (NAC). Lastly, we show by orthogonal chemical genetics that Ypl225w primes eEF1A nascent chains for their subsequent binding to GTP and release from Ypl225w. Our work establishes eEF1A as a model system for chaperone-dependent co-translational folding and unveils a novel mechanism for GTP-driven folding on the ribosome.
HostingRepository	PRIDE
AnnounceDate	2025-02-05
AnnouncementXML	Submission_2025-02-05_06:36:16.305.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058955
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ibrahim Sabbarini
SpeciesList	scientific name: Saccharomyces cerevisiae; NCBI TaxID: NCBITaxon:4932; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-17 15:53:12	ID requested
⏵ 1	2025-02-05 06:36:24	announced

10.1038/s41467-025-56489-3;

Sabbarini IM, Reif D, Park K, McQuown AJ, Nelliat AR, Trejtnar C, D, ö, tsch V, Shakhnovich EI, Murray AW, Denic V, A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A. Nat Commun, 16(1):1277(2025) [pubmed]

10.6019/PXD058955;

submitter keyword: Yeast, Ypl225w

Vladimir Denic
contact affiliation	Harvard University MCB Department
contact email	vlad.denic@gmail.com
lab head
Ibrahim Sabbarini
contact affiliation	Harvard University
contact email	isabbarini@fas.harvard.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/2025/02/PXD058955

PRIDE project URI

• PRIDE
  1. PXD058955
     1. Label: PRIDE project
     2. Name: Ypl225w-3xFLAG IP-mass spectrometry