6w10

Structure of mouse TREX1 with E198K disease-associated mutationStructure of mouse TREX1 with E198K disease-associated mutation

Structural highlights 6w10 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8000338Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TREX1_MOUSE Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair. Publication Abstract from PubMed Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for the immune response to cancer and pathogen infection. Here, we discover that cGAS-DNA phase separation is required to resist negative regulation and allow efficient sensing of immunostimulatory DNA. We map the molecular determinants of cGAS condensate formation and demonstrate that phase separation functions to limit activity of the cytosolic exonuclease TREX1. Mechanistically, phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to an outer shell at the droplet periphery. We identify a TREX1 mutation associated with the severe autoimmune disease Aicardi-Goutieres syndrome that increases penetration of TREX1 into the repressive droplet interior and specifically impairs degradation of phase-separated DNA. Our results define a critical function of cGAS-DNA phase separation and reveal a molecular mechanism that balances cytosolic DNA degradation and innate immune activation. cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing.,Zhou W, Mohr L, Maciejowski J, Kranzusch PJ Mol Cell. 2021 Feb 18;81(4):739-755.e7. doi: 10.1016/j.molcel.2021.01.024. PMID:33606975 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Exonuclease 3D structures

spinqualitylabelsall models 6w10, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image