PXD052597

PXD052597 is an original dataset announced via ProteomeXchange.

Title	Impact of Folded-State Protein Filaments on the Yeast Proteome
Description	The formation of large polymeric structures without protein unfolding and aggregation, such as cytoskeletal and enzyme filaments, is crucial for normal cellular function. We term this type of assembly agglomeration in contrast to protein aggregation caused by protein misfolding. Several agglomeration-associated diseases, such as sickle cell disease, are caused by hemoglobin agglomeration. Nevertheless, it is still unknown whether there is a specific machinery to recognize protein agglomeration and how agglomeration affects cell – is it as harmful as aggregation or relatively neutral? To address this question, we performed shotgun proteomics of wild-type dihedral homomeric proteins and their mutated counterparts prone to aggregation or agglomeration in yeasts. We identified lower expression of both the exogenous construct and YFP in the misfolded variants of all three constructs when compared to their wild type and agglomerate counterparts (Fig. 4A-B, Sup Fig. 9D-E). Surprisingly, they were the only differentially expressed proteins in both 1POK variants and 1M3U variants. On the contrary, in 2VYC there were many differentially expressed proteins between its variants (Fig. 4C-D). In the misfolded variant, we detected the decrease in 2VYC and YFP expression was coupled with an increase in chaperone proteins (HSP104/HSP78/HSP42/SSA4/STI1, Fig 4C, Sup Fig. 10). GO-SLIM analysis showed enrichment in the upregulated genes for four categories; ‘protein-folding’ (P.value < 0.0002), ‘response to heat’ (P.value < 0.0016), ‘response to oxidative stress’ (P.value < 0.0352) and ‘oligosaccharide metabolic process’ (P.value < 0.0445). Looking at the agglomerate, we focused on proteins that are differentially expressed uniquely in the agglomerate mutant but don’t change in the misfolded mutant. We detected several cell wall related proteins that were upregulated (DCW1/GAS1/GAS3/NPP1) [71–73] as well as proteins localized to the bud neck (PAL1/RAX2) [74,75]. We also detected an increase in the prion progenitor RNQ1. In the down regulated proteins, we identified several metabolic enzymes and among them CYS4 which forms filaments [10]. Other down regulated proteins relate to cell polarity and especially actin polarization (CDC42/LST8/PHO85/RHO4) [76–79]. We detected three protein categories that were enriched in the upregulated genes; ‘cell budding’ (P.value < 0.0334), ‘cell wall organization or biogenesis’ (P.value < 0.0396) and ‘chromatin organization’ (P.value < 0.0441). In the downregulated genes three categories were also enriched; ‘carbohydrate metabolic process’ (P.value < 0.00363), ‘generation of precursor metabolites and energy’ (P.value < 0.0154) and ‘monocarboxylic acid metabolic process’ (P.value < 0.0427)
HostingRepository	PRIDE
AnnounceDate	2025-08-21
AnnouncementXML	Submission_2025-08-21_12:13:38.275.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD052597
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Arseniy Lobov
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-27 10:18:39	ID requested
⏵ 1	2025-08-21 12:13:38	announced

10.6019/PXD052597;

submitter keyword: Aggregation, agglomeration, yeasts, filaments, proteostasis

Emmanuel Levy
contact affiliation	Dept. of Molecular and Cellular Biology, University of Geneva
contact email	Emmanuel.Levy@unige.ch
lab head
Arseniy Lobov
contact affiliation	Yifat Merbl Lab, Dept. of Systems Immunology, Weizmann Institute of Science
contact email	arseniylobov@gmail.com
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/2025/08/PXD052597

PRIDE project URI

• PRIDE
  1. PXD052597
     1. Label: PRIDE project
     2. Name: Impact of Folded-State Protein Filaments on the Yeast Proteome