Antigenic peptide trimming by ER aminopeptidases—Insights from structural studies

• ERAP1 and ERAP2 process antigenic peptides and can regulate antigen presentation.
• The molecular mechanisms are complex and poorly understood.
• Several recent crystallographic structures have just been released for these enzymes.
• These structures provide novel insight onto the mechanism of these enzymes and their role in disease.

Generation and destruction of antigenic peptides by ER resident aminopeptidases ERAP1 and ERAP2 have been shown in the last few years to be important for the correct functioning and regulation of the adaptive immune response. These two highly homologous aminopeptidases appear to have evolved complex mechanisms well suited for their biological role in antigen presentation. Furthermore, polymorphic variability in these enzymes appears to affect their function and predispose individuals to disease. This review discusses our current understanding of the molecular mechanisms behind ERAP1/2 function as suggested by several recently determined crystallographic structures of these enzymes.