4F9G

Crystal structure of STING complex with Cyclic di-GMP.

Summary for 4F9G

• Entry DOI: 10.2210/pdb4f9g/pdb
• Related: 4F9E
• Descriptor: Transmembrane protein 173, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one) (2 entities in total)
• Functional Keywords: interferon, immune system c-di-gmp dimerisation, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q86WV6
• Total number of polymer chains: 2
• Total formula weight: 60387.34

Authors

Kabaleeswaran, V.,Wu, H. (deposition date: 2012-05-18, release date: 2012-07-25, Last modification date: 2023-09-13)

Primary citation

Yin, Q.,Tian, Y.,Kabaleeswaran, V.,Jiang, X.,Tu, D.,Eck, M.J.,Chen, Z.J.,Wu, H.
Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING.
Mol.Cell, 46:735-745, 2012

PubMed Abstract: Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an α + β fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.

PubMed: 22705373
DOI: 10.1016/j.molcel.2012.05.029

Experimental method

X-RAY DIFFRACTION (2.95 Å)