6A06

Structure of pSTING complex

Summary for 6A06

• Entry DOI: 10.2210/pdb6a06/pdb
• Descriptor: Stimulator of interferon genes protein, SULFATE ION, cGAMP, ... (4 entities in total)
• Functional Keywords: psting, signaling protein
• Biological source: Sus scrofa (Pig)
• Total number of polymer chains: 2
• Total formula weight: 46726.19

Authors

Yuan, Z.L.,Shang, G.J.,Cong, X.Y.,Gu, L.C. (deposition date: 2018-06-05, release date: 2019-06-19, Last modification date: 2024-03-27)

Primary citation

Cong, X.,Yuan, Z.,Du, Y.,Wu, B.,Lu, D.,Wu, X.,Zhang, Y.,Li, F.,Wei, B.,Li, J.,Wu, J.,Xu, S.,Wang, J.,Qi, J.,Shang, G.,Gu, L.
Crystal structures of porcine STINGCBD-CDN complexes reveal the mechanism of ligand recognition and discrimination of STING proteins.
J.Biol.Chem., 294:11420-11432, 2019

PubMed Abstract: The cyclic dinucleotide (CDN)-imulator of terferon enes (STING) pathway plays an important role in the detection of viral and bacterial pathogens in animals. Previous studies have shown that the metazoan second messenger cyclic [G(2',5')pA(3',5')p] (2',3'-cGAMP) generated by cyclic GMP-AMP synthase cGAS binds STING with high affinity compared with bacterial CDNs such as c-di-GMP, c-di-AMP, and 3',3'-cGAMP. Despite recent progress indicating that the CDN-binding domain (CBD) of dimeric STING binds asymmetric 2',3'-cGAMP preferentially over symmetric 3',3'-CDNs, it remains an open question whether STING molecules, such as human STING, adopt a symmetric dimeric conformation to efficiently engage its asymmetric ligand. Here, structural studies of the CBD from porcine STING (STING) in complex with CDNs at 1.76-2.6 Å resolution revealed that porcine STING, unlike its human and mouse counterparts, can adopt an asymmetric ligand-binding pocket to accommodate the CDNs. We observed that the extensive interactions and shape complementarity between asymmetric 2',3'-cGAMP and the ligand-binding pocket make it the most preferred ligand for porcine STING and that geometry constraints limit the binding between symmetric 3',3'-CDN and porcine STING. The ligand-discrimination mechanism of porcine STING observed here expands our understanding of how the CDN-STING pathway is activated and of its role in antiviral defense.

PubMed: 31167783
DOI: 10.1074/jbc.RA119.007367

Experimental method

X-RAY DIFFRACTION (1.792 Å)