In this new paper we describe the analysis of the enzymatic properties of the autoimmunity-protective allotype 10 of ER aminopeptidase 1 (ERAP1) and its unique SNPs at locations 349 and 725. ERAP1 is a polymorphic intracellular aminopeptidase with key roles in antigen presentation and adaptive immune responses. Our results suggest that allotype 10 is not just an inactive variant of ERAP1 but rather carries distinct enzymatic properties that largely stem from changes at positions 349 and 725. These changes affect kinetic and thermodynamic parameters that likely control rate-limiting steps in the catalytic cycle, resulting in an enzyme optimized for sparing small substrates and contributing to the homeostasis of antigenic epitopes in the ER. 

Read it here: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1415964/full