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