Structural basis of human TREX1 DNA degradation and autoimmune disease.

ABSTRACT: TREX1 is a cytosolic DNA nuclease essential for regulation of cGAS-STING immune signaling. Existing structures of mouse TREX1 establish a mechanism of DNA degradation and provide a key model to explain autoimmune disease, but these structures incompletely explain human disease-associated mutations and have limited ability to guide development of small-molecule therapeutics. Here we determine crystal structures of human TREX1 in apo and DNA-bound conformations that provide high-resolution detail of all human-specific features. A 1.25 Å structure of human TREX1 establishes a complete model of solvation of the exonuclease active site and a 2.2 Å structure of the human TREX1-DNA complex enables identification of specific substitutions involved in DNA recognition. We map each TREX1 mutation ass

SUBMITTER: Zhou W 

PROVIDER: S-EPMC9314330 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature