PXD039584 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-01-20 03:33:18 | ID requested | |
⏵ 1 | 2023-11-21 07:59:40 | announced | |
Publication List
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; |
Keyword List
submitter keyword: HLA, MHC class1, inhibitor,ERAP1, aminopetidase, Immunopeptidomics, allosteric |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039584
- Label: PRIDE project
- Name: Distinct modulation of cellular immunopeptidome by the allosteric regulatory site of ER aminopeptidase 1