title: Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum.
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.
authors.affiliation: Institut National de la Sante et Recherche Médicale Unité 580, Université René Descartes Paris 5, 75015 Paris, France.
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
authors.forename: Oliver
authors.initials: O
authors.lastname: Carroll
authors.forename: Vivian
authors.initials: V
authors.lastname: Lindo
authors.forename: Margarita
authors.initials: M
authors.lastname: Del Val
authors.forename: Daniel
authors.initials: D
authors.lastname: Lopez
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepelletier
authors.forename: Fiona
authors.initials: F
authors.lastname: Greer
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Doriana
authors.initials: D
authors.lastname: Fruci
authors.forename: Gabriele
authors.initials: G
authors.lastname: Niedermann
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Endert
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017951:Antigen Presentation / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008861:Microsomes; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments; D012313:RNA; D000626:Aminopeptidases; C464841:ERAP1 protein, human