Activation of STING by Endogenous cGAMP

In a paper published online in Molecular Cell on June 3rd, 2013, we report the identification of a cyclic GMP-AMP isomer containing both 2’-5’ and 3’-5’ phosphodiester linkages (2'3'-cGAMP) as the endogenous second messenger generated by the cytosolic DNA sensor cGAS. Further, we solve the crystal structure of STING bound to the cGAS product, which explains the high affinity interaction between STING and 2’3’-cGAMP, and reveals a ligand-induced conformational change of STING that may underlie its activation. For details see:

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

Congratulations to Xu, Heping, Jiaxi, Xuewu, Josh, Chuo and James!