6DNK
Human Stimulator of Interferon Genes
Summary for 6DNK
| Entry DOI | 10.2210/pdb6dnk/pdb |
| Descriptor | Stimulator of interferon genes protein, cGAMP (3 entities in total) |
| Functional Keywords | human sting, complex, 2', 3'-cgamp, tmem173, ala230 allelle, 230a/232r, immune system |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 21772.13 |
| Authors | Fernandez, D.,Li, L.,Ergun, S.L. (deposition date: 2018-06-06, release date: 2019-03-13, Last modification date: 2023-10-11) |
| Primary citation | Ergun, S.L.,Fernandez, D.,Weiss, T.M.,Li, L. STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition. Cell, 178:290-301.e10, 2019 Cited by PubMed Abstract: How the central innate immune protein, STING, is activated by its ligands remains unknown. Here, using structural biology and biochemistry, we report that the metazoan second messenger 2'3'-cGAMP induces closing of the human STING homodimer and release of the STING C-terminal tail, which exposes a polymerization interface on the STING dimer and leads to the formation of disulfide-linked polymers via cysteine residue 148. Disease-causing hyperactive STING mutations either flank C148 and depend on disulfide formation or reside in the C-terminal tail binding site and cause constitutive C-terminal tail release and polymerization. Finally, bacterial cyclic-di-GMP induces an alternative active STING conformation, activates STING in a cooperative manner, and acts as a partial antagonist of 2'3'-cGAMP signaling. Our insights explain the tight control of STING signaling given varying background activation signals and provide a therapeutic hypothesis for autoimmune syndrome treatment. PubMed: 31230712DOI: 10.1016/j.cell.2019.05.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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