3SE6

Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2

Summary for 3SE6

• Entry DOI: 10.2210/pdb3se6/pdb
• Descriptor: Endoplasmic reticulum aminopeptidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: thermolysin-like catalytic domain, aminopeptidase, zinc binding, glycosylation, endoplasmic reticulum, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 226107.54

Authors

Birtley, J.R.,Saridakis, E.,Stratikos, E.,Mavridis, I.M. (deposition date: 2011-06-10, release date: 2011-12-21, Last modification date: 2024-11-20)

Primary citation

Birtley, J.R.,Saridakis, E.,Stratikos, E.,Mavridis, I.M.
The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing.
Biochemistry, 51:286-295, 2012

PubMed Abstract: Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 cooperate to trim a vast variety of antigenic peptide precursors to generate mature epitopes for binding to major histocompatibility class I molecules. We report here the first structure of ERAP2 determined at 3.08 Å by X-ray crystallography. On the basis of residual electron density, a lysine residue has been modeled in the active site of the enzyme; thus, the structure corresponds to an enzyme-product complex. The overall domain organization is highly similar to that of the recently determined structure of ERAP1 in its closed conformation. A large internal cavity adjacent to the catalytic site can accommodate large peptide substrates. The ERAP2 structure provides a structural explanation for the different peptide N-terminal specificities between ERAP1 and ERAP2 and suggests that such differences extend throughout the whole peptide sequence. A noncrystallographic dimer observed may constitute a model for a proposed ERAP1-ERAP2 heterodimer. Overall, the structure helps explain how two homologous aminopeptidases cooperate to process a large variety of sequences, a key property of their biological role.

PubMed: 22106953
DOI: 10.1021/bi201230p

Experimental method

X-RAY DIFFRACTION (3.08 Å)