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|3mdj, resolution 2.95Å ()|
|Ligands:||, , , ,|
|Gene:||ERAP1, APPILS, ARTS1, KIAA0525, UNQ584/PRO1154 (Homo sapiens)|
ER Aminopeptidase, ERAP1, Bound to the Zinc Aminopeptidase Inhibitor, Bestatin
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.
Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1., Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ, Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864 doi:10.1038/nsmb.2021