Premium
Strucutral Characterization of ER aminopeptidase, ERAP1
Author(s) -
Nguyen Tina T,
Stern Lawrence J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a471
Subject(s) - epitope , mhc class i , major histocompatibility complex , aminopeptidase , antigen presentation , amino acid , chemistry , biology , antigen , microbiology and biotechnology , biochemistry , genetics , leucine , cytotoxic t cell , in vitro
The endoplasmic reticulum (ER) aminopeptidase, ERAP1, is a 941 amino acid member of the M1 family of zinc metalloaminopeptidases. Unlike other aminopeptidases, ERAP1 exhibits a substrate length preference and a C‐terminal residue preference. ERAP1 has been suggested to have a molecular ruler mechanism because it trims peptides to lengths (8 or 9 amino acids) matching those required for binding into the peptide binding groove of class I major histocompatibility complex (MHC) molecules. ERAP1 activity has been shown to affect class I MHC antigen presentation. Treatment with interferon gamma (IFN‐γ), an immunologically relevant cytokine, upregulates the expression of ERAP1 in cells. Knock‐down of ERAP1 by siRNA results in less overall antigenic presentation during IFN‐γ treatment, although the knock‐down does not affect all class I MHC epitopes. Our CD spectroscopy studies suggest that ERAP1 is about 30% helical, and we have obtained low resolution x‐ray crystal data. Further crystallographic studies will be conducted to resolve the structure of ERAP1 in order to explore the structural basis of the unique enzymatic characteristics of ERAP1. This research was supported by grant # NIH‐RO1‐AI38996.