Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease

► In this study we determine the crystal structures of TREX1 mutants linked to autoimmune disease. ► The structures reveal changes in the architecture of the active site that explain loss of catalytic activity. ► The structures also reveal conformational movement that is required for catalytic activity. ► Based on our cumulative work we propose a mechanism for catalysis for TREX1. ► The structures provide insight into dysfunction relating to human disease.