Final Activity Report Summary - ERAP1 (Structural basis and specificity of antigenic peptide trimming by the newly discoverd ER aminopeptidases ERAP1 and ERAP2)
This project's goal was to contribute to our understanding on the mechanism of function of those aminopeptidases and their role in antigenic peptide generation. Significant progress was done in determining the three-dimensional structure of ERAP1, the most important of those aminopeptidases, a step necessary for understanding its function. Systematic analysis of ERAP1's specificity has led to surprising results that suggest that this enzyme has strong preferences for some peptides versus others. This finding can help us understand the in vivo effects of ERAP1 down-regulation seen in mouse models. Overall, the findings from this project appear to provide a molecular framework for understanding a new and crucial layer of regulation of immune response that is involved to predisposition to autoimmunity and cancer.