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Structural Basis For Antigenic Peptide Precursor Processing by the Endoplasmic Reticulum Aminopeptidase ERAP1
Author(s) -
Nguyen Tina T,
Chang ShihChung,
Evnouchidou Irini,
York Ian,
Zikos Christos,
Rock Kenneth L.,
Goldberg Alfred L,
Stratikos Efstratios,
Stern Lawrence J
Publication year - 2011
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.25.1_supplement.lb72
Subject(s) - endoplasmic reticulum , peptide , aminopeptidase , trimming , chemistry , residue (chemistry) , antigen , enzyme , protein structure , biochemistry , structural biology , stereochemistry , biology , amino acid , genetics , leucine , computer science , operating system
ERAP1 trims antigen precursors to fit into MHC class I proteins. To perform this function, ERAP1 has unique substrate preferences, trimming long peptides while sparing shorter ones. To identify the structural basis for ERAP1's unusual properties, we determined the X‐ray crystal structure of human ERAP1 bound to bestatin. The structure reveals an open conformation with a large interior compartment. An extended groove originating from the enzyme's catalytic center can accommodate long peptides and has features that explain ERAP1's broad specificity for antigenic peptide precursors. Structural and biochemical analysis suggest a mechanism for ERAP1's length‐dependent trimming activity, whereby binding of long but not short substrates induces a conformational change with reorientation of a key catalytic residue towards the active site. ERAP1's unique structural elements suggest how a generic aminopeptidase structure has been adapted for the specialized function of trimming antigenic precursors.