Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2)
| Autor: | Daniel López, B Galocha, Miguel G. Fontela, Eilon Barnea, Pilar Lauzurica, Carmen Mir, Arie Admon, Antonio J. Martín-Galiano, Elena Lorente |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Israel Science Foundation |
| Rok vydání: | 2020 |
| Předmět: |
Proteome
Sequence alignment Peptide Human leukocyte antigen Endoplasmic Reticulum Ligands Biochemistry Campylobacter jejuni Aminopeptidase Aminopeptidases Analytical Chemistry Cell Line 03 medical and health sciences Gene Knockout Techniques Tandem Mass Spectrometry Humans Spondylitis Ankylosing Amino Acid Sequence Molecular Biology Alleles HLA-B27 Antigen 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Chemistry Endoplasmic reticulum Research 030302 biochemistry & molecular biology Computational Biology biology.organism_classification Endoplasmic reticulum aminopeptidase 2 HLA-B High-Throughput Screening Assays Peptides Hydrophobic and Hydrophilic Interactions Sequence Alignment |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) Mol Cell Proteomics |
| Popis: | The mass spectrometry data have been deposited to the MassIVE repository (http://massive.ucsd.edu) with the data set identifier MSV000084718. The HLA-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with AS, a chronic inflammatory spondyloarthropathy. This study examined the effect of ERAP2 in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones, and the peptides were identified using high-throughput mass spectrometry analyses. The relative abundance of a thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in the presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of the antigen-binding site of the HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and PΩ positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease. Ministerio de Ciencia, Innovación y Universidades (MPY 388/18, MPY 483 1346/16, SAF2014–58052) Israel Science Foundation (No. 1435/16) Sí |
| Databáze: | OpenAIRE |
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