title: The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing.
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.
authors: Structural and Supramolecular Chemistry Laboratory, Institute of Physical Chemistry, National Center for Scientific Research Demokritos, Aghia Paraskevi 15310, Athens, Greece.
authors: James R
authors: JR
authors: Birtley
authors: Emmanuel
authors: E
authors: Saridakis
authors: Efstratios
authors: E
authors: Stratikos
authors: Irene M
authors: IM
authors: Mavridis
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017951:Antigen Presentation / Q000276:immunology*; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000276:immunology*; D006031:Glycosylation; D006680:HLA Antigens / Q000737:chemistry / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000502:physiology; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000502:physiology; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D011498:Protein Precursors; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human