Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases

In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e79596-e79596
Main Authors: Lorente, Elena, Barriga, Alejandro, Johnstone, Carolina, Mir, Carmen, Jiménez, Mercedes, López, Daniel
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aminopeptidase
Aminopeptidases
Aminopeptidases - chemistry
Aminopeptidases - metabolism
Antigen presentation
Antigen processing
Antigens
Barnea
Cytotoxicity
Degradation products
Endoplasmic reticulum
Enzymes
Health aspects
Histocompatibility antigen HLA
Histocompatibility antigens
HLA histocompatibility antigens
HLA-B27 Antigen - metabolism
Humans
Ions
Leukocytes
Ligands
Mass spectrometry
Mass spectroscopy
Minor Histocompatibility Antigens
Molecular Sequence Data
Peptides
Proteasomes
Protein Multimerization
Protein Structure, Quaternary
Proteins
Proteolysis
Respiratory syncytial virus
Respiratory Syncytial Virus, Human - metabolism
Scientific imaging
Substrates
Trimming
Viral Proteins - chemistry
Viral Proteins - metabolism
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Summary:In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0079596