TY - JOUR
T1 - Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum
AU - Saveanu, Loredana
AU - Carroll, Oliver
AU - Lindo, Vivian
AU - Del Val, Margarita
AU - Lopez, Daniel
AU - Lepelletier, Yves
AU - Greer, Fiona
AU - Schomburg, Lutz
AU - Fruci, Doriana
AU - Niedermann, Gabriele
AU - Van Endert, Peter M.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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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U2 - 10.1038/ni1208
DO - 10.1038/ni1208
M3 - Article
C2 - 15908954
AN - SCOPUS:22144442460
VL - 6
SP - 689
EP - 697
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 7
ER -