3MDJ

ER Aminopeptidase, ERAP1, Bound to the Zinc Aminopeptidase Inhibitor, Bestatin

Summary for 3MDJ

• Entry DOI: 10.2210/pdb3mdj/pdb
• Descriptor: Endoplasmic reticulum aminopeptidase 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: aminopeptidase, zn binding protein, er, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 319747.22

Authors

Nguyen, T.T.,Stern, L.J. (deposition date: 2010-03-30, release date: 2011-03-30, Last modification date: 2024-11-27)

Primary citation

Nguyen, T.T.,Chang, S.C.,Evnouchidou, I.,York, I.A.,Zikos, C.,Rock, K.L.,Goldberg, A.L.,Stratikos, E.,Stern, L.J.
Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.
Nat.Struct.Mol.Biol., 18:604-613, 2011

PubMed 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.

PubMed: 21478864
DOI: 10.1038/nsmb.2021

Experimental method

X-RAY DIFFRACTION (2.95 Å)