Title : Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum
aminopeptidase ERAP1
Abstract :
- ERAP1 trims antigen precursors to fit into MHC class I proteins
- To fulfill this function, ERAP1 has unique substrate preferences, trimming long peptides but 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 analyses suggest a mechanism for ERAP1 's length-dependent trimming activity, whereby binding of long rather than short substrates induces a conformational change with reorientation of a key catalytic residue toward 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