PXD039584

PXD039584 is an original dataset announced via ProteomeXchange.

Title	Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1
Description	ER aminopeptidase 1 (ERAP1) is an ER-resident aminopeptidase that excises N-terminal residues off peptides that then bind onto Major Histocompatibility Complex I molecules (MHC-I) and indirectly modulates adaptive immune responses. ERAP1 contains an allosteric regulatory site that accommodates the C-terminus of only some peptide substrates, raising questions about its exact influence on antigen presentation and the potential of allosteric inhibition for cancer immunotherapy. We used an inhibitor that targets this regulatory site to study its effect on the immunopeptidome of a human cancer cell line. The immunopeptidomes of allosterically inhibited and ERAP1 knockout cells contain high-affinity peptides with sequence motifs consistent with the cellular HLA class I haplotypes, but were strikingly different in peptide composition. Compared to knockout cells, allosteric inhibition did not affect the length distribution of peptides and skewed the peptide repertoire both in terms of sequence motifs and HLA allele utilization, indicating significant mechanistic differences between the two ways of disrupting ERAP1 function. These findings suggest that the regulatory site of ERAP1 plays distinct roles in antigenic peptide selection, which should be taken into consideration when designing therapeutic interventions targeting the cancer immunopeptidome.
HostingRepository	PRIDE
AnnounceDate	2023-11-21
AnnouncementXML	Submission_2023-11-21_07:59:38.364.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-20 03:33:18	ID requested
⏵ 1	2023-11-21 07:59:40	announced

Temponeras I, Samiotaki M, Koumantou D, Nikopaschou M, Kuiper JJW, Panayotou G, Stratikos E, Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1. Eur J Immunol, 53(8):e2350449(2023) [pubmed]

10.1002/eji.202350449;

submitter keyword: HLA, MHC class1, inhibitor,ERAP1, aminopetidase, Immunopeptidomics, allosteric

Efstratios Stratikos
contact affiliation	Department of Chemistry, National and Kapodistrian University of Athens, 15784 Zografou, Greece National Centre for Scientific Research Demokritos, Agia Paraskevi, Greece
contact email	estratikos@chem.uoa.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
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/2023/11/PXD039584

PRIDE project URI

• PRIDE
  1. PXD039584
     1. Label: PRIDE project
     2. Name: Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1