Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum.
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.
Saveanu
Loredana
L
Institut National de la Sante et Recherche Médicale Unité 580, Université René Descartes Paris 5, 75015 Paris, France.
Carroll
Oliver
O
Lindo
Vivian
V
Del Val
Margarita
M
Lopez
Daniel
D
Lepelletier
Yves
Y
Greer
Fiona
F
Schomburg
Lutz
L
Fruci
Doriana
D
Niedermann
Gabriele
G
van Endert
Peter M
PM
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
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments; D012313:RNA; D000626:Aminopeptidases; C464841:ERAP1 protein, human