PXD012348

PXD012348 is an original dataset announced via ProteomeXchange.

Title	Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behçet’s Disease-Associated HLA-B*51 Peptidome
Description	The endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to be loaded onto HLA molecules, including the main risk factor for Behçet’s disease HLA-B*51. ERAP1 is also a risk factor among HLA-B*51-positive individuals, whereas no association is known with ERAP2. This study addressed the mutual relationships between both enzymes in the processing of an HLA-bound peptidome, interrogating their differential association with Behçet’s disease. CRISPR/Cas9 was used to generate knock outs of ERAP1, ERAP2 or both from transfectant 721.221-HLA-B*51:01 cells. The surface expression of HLA-B*51 was reduced in all cases. The effects of depleting each or both enzymes on the B*51:01 peptidome were analyzed by quantitative label-free mass spectrometry. Substantial quantitative alterations of peptide length, subpeptidome balance, N-terminal residue usage, affinity and presentation of non-canonical ligands were observed. These effects were often different in the presence or absence of the other enzyme, revealing their mutual dependency. In the absence of ERAP1, ERAP2 showed similar and significant processing of B*51:01 ligands, indicating functional redundancy. The high overlap between the peptidomes of wildtype and double KO cells indicates that a large majority of B*51:01 ligands are present in the ER even in the absence of ERAP1/ERAP2. These results indicate that both enzymes have distinct, but complementary and partially redundant effects on the B*51:01 peptidome, leading to its optimization and maximal surface expression. The distinct effects of both enzymes on the HLA-B*51 peptidome provide a basis for their differential association with Behçet’s disease and suggest a pathogenetic role of the B*51:01 peptidome.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:55:25.662.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eilon Barnea
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-15 03:45:36	ID requested
1	2019-05-20 01:02:31	announced
⏵ 2	2024-10-22 04:55:28	announced	2024-10-22: Updated project metadata.

Guasp P, Lorente E, Mart, í, n-Esteban A, Barnea E, Romania P, Fruci D, Kuiper JW, Admon A, L, ó, pez de Castro JA, Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-associated HLA-B*51 Peptidome. Mol Cell Proteomics, 18(8):1491-1510(2019) [pubmed]

10.1074/mcp.ra119.001515;

submitter keyword: HLA-B*51, ERAP1, Behçet’s Disease, ERAP2, peptidome

Arie Admon
contact affiliation	Faculty of Biology, Technion - Israel Institute of Technology
contact email	admon@technion.ac.il
lab head
Eilon Barnea
contact affiliation	Technion
contact email	eilonb@tx.technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012348
     1. Label: PRIDE project
     2. Name: Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behçet’s Disease-Associated HLA-B*51 Peptidome