PXD052314

PXD052314 is an original dataset announced via ProteomeXchange.

Title	A549 adenocarcinoma human alveolar basal epithelial cells Salmonella enterica infection Proteomics
Description	For decades, the prevailing paradigm has posited that the primary function of proteasome-derived peptides is serving for antigen presentation. The proteasome-cleaved peptides are loaded onto Major Histocompatibility Complex I (MHCI) molecules and serve to elicit T cell-mediated cytotoxicity. Yet, whether the products of proteasomal degradation may play additional roles in modulating immune responses, remains largely unknown. Antimicrobial peptides (AMPs) serve as a first line of defense against invading pathogens. They act quickly to prevent the establishment of infections, providing an initial barrier against microbes before the adaptive immune system can respond. As such, there is a great need in constitutive and bacterial-induced production of AMPs, across numerous tissues. As AMPs are widely distributed across the proteome and may not be readily clipped from their host proteins, degradation mechanisms may facilitate their release and diversity. In this study, we uncover a role for cellular proteasomes in the constitutive generation of proteasome-derived defense peptides (PDDPs) capable of impeding bacterial growth in vitro and in vivo by disrupting bacterial membranes. Further, we found that in response to bacterial infection, the composition and function of cellular proteasomes are altered. Specifically, recruitment of the regulatory cap, PSME3 onto proteasomes, increases tryptic-like cleavages of peptides, which in turn, enhances the production of PDDPs with cationic termini as a defense mechanism. In silico prediction of proteome-wide proteasomal cleavage identified more than 270,000 putative peptides that may be generated en route to degradation and bear cationic properties to serve as a first line of defense. Our findings suggest that PDDPs play a previously unrecognized fundamental role in cell-autonomous innate immunity against pathogens.
HostingRepository	PRIDE
AnnounceDate	2025-03-07
AnnouncementXML	Submission_2025-03-07_02:03:17.822.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yifat Merbl
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	mono N-acetylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-16 05:55:29	ID requested
⏵ 1	2025-03-07 02:03:18	announced

10.1038/S41586-025-08615-W;

submitter keyword: infection, proteomics

Yifat Merbl
contact affiliation	Systems Immunology Department, The Merbl Lab, Weizmann Institute of Science, Israel
contact email	yifat.merbl@weizmann.ac.il
lab head
Yifat Merbl
contact affiliation	Weizmann Institute of Science
contact email	merbllab@weizmann.ac.il
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/2025/03/PXD052314

PRIDE project URI

• PRIDE
  1. PXD052314
     1. Label: PRIDE project
     2. Name: A549 adenocarcinoma human alveolar basal epithelial cells Salmonella enterica infection Proteomics