Cited by 482vaccines and immunoinformatics approachesPeptidase Inhibition and AnalysisImmunotherapy and Immune Responses

Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum

Saveanu, Loredana, Carroll, Oliver, Lindo, Vivian, Del Val, Margarita, Lopez, Daniel, Lepelletier, Yves, Greer, Fiona, Schomburg, Lutz +3 more·2005·Nature Immunology

Abstract

The generation of many HLA class I peptides entails a final trimming step in the endoplasmic reticulum that, in humans, is accomplished by two 'candidate' aminopeptidases. We show here that one of these, ERAP1, was unable to remove several N-terminal amino acids that were trimmed efficiently by the second enzyme, ERAP2. This trimming of a longer peptide required the concerted action of both ERAP1 and ERAP2, both for in vitro digestion and in vivo for cellular antigen presentation. ERAP1 and ERAP2 localized together in vivo and associated physically in complexes that were most likely heterodimeric. Thus, the human endoplasmic reticulum is equipped with a pair of trimming aminopeptidases that have complementary functions in HLA class I peptide presentation.

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Crossref · 10.1038/ni1208

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Authors
Saveanu, L., Carroll, O., Lindo, V., Del Val, M., Lopez, D., Lepelletier, Y., Greer, F., Schomburg, L., Fruci, D., Niedermann, G., & van Endert, P. M.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Charité – Universitätsmedizin Berlin (DE)
  • Max Planck Society (DE)
Venue
Nature Immunology
Published
2005-05-22
Volume
6
Issue
7
Pages
689-697
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W1981338942
Cited by
481
References
35
Citations by year
2026: 8 · 2025: 18 · 2024: 18 · 2023: 31 · 2022: 20 · 2021: 23 · 2020: 28 · 2019: 30 · 2018: 25 · 2017: 25 · 2016: 15 · 2015: 26 · 2014: 25 · 2013: 31 · 2012: 27
FWCI
7.65
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
Funders
  • Comunidad de Madrid
  • European Commission
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
ERAP1, ERAP2, aminopeptidase, peptide trimming, HLA class I, endoplasmic reticulum, antigen presentation
MeSH terms
Aminopeptidases, Epitopes, Endoplasmic Reticulum, HeLa Cells, Humans, Microsomes, Peptide Fragments, RNA, Immunoblotting, Histocompatibility Antigens Class I, Minor Histocompatibility Antigens, Antigen Presentation, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference

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