Extended Data Fig. 7: Additional mutational analyses of the activation of STING by C53 and cGAMP.

a, C53 could induce phosphorylation of the R238A/Y240A mutant of STING in cells, which has its cGAMP-pocket disrupted and could not be activated by cGAMP. b, M120L, a mutation in the C53-binding pocket, reduced STING phosphorylation when cells were stimulated with cGAMP at a lower concentration (100 nM). c, L30A, a mutation in TMD–TMD oligomerization interface, reduced STING phosphorylation when cells were stimulated with cGAMP at a lower concentration (100 nM). These effects of M120L and L30A were suppressed when cells were treated with cGAMP at 1,000 nM. These results suggest that both the TMD pocket and the TMD–TMD interface are important for cGAMP-mediated activation of STING, although high concentrations of cGAMP can overcome the detrimental effects of some mutations in these regions. The experiments were carried out in a similar manner as in Figs. 3, 4, and the results shown are representative of three biological repeats. For gel source data, see Supplementary Fig. 1.