PDBsum entry 6a06

Signaling protein

PDB id: 6a06

Contents

Protein chains

188 a.a.

Ligands

SO4 ×4

1SY

Waters ×233

PDB id:

6a06

Name:

Signaling protein

Title:

Structure of psting complex

Structure:

Stimulator of interferon genes protein. Chain: a, b. Synonym: posting,transmembrane protein 173. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Gene: tmem173, sting. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.79Å R-factor: 0.178 R-free: 0.220

Authors:

Z.L.Yuan,G.J.Shang,X.Y.Cong,L.C.Gu

Key ref:

X.Cong et al. (2019). Crystal structures of porcine STING^CBD-CDN complexes reveal the mechanism of ligand recognition and discrimination of STING proteins. J Biol Chem, 294, 11420-11432. PubMed id: 31167783 DOI: 10.1074/jbc.RA119.007367

Date:

05-Jun-18 Release date: 19-Jun-19

Protein chains

B8XX90  (STING_PIG) -  Stimulator of interferon genes protein from Sus scrofa

Seq: 378 a.a.

Struc: 188 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.RA119.007367

J Biol Chem 294:11420-11432 (2019)

PubMed id: 31167783

Crystal structures of porcine STING^CBD-CDN complexes reveal the mechanism of ligand recognition and discrimination of STING proteins.

X.Cong, Z.Yuan, Y.Du, B.Wu, D.Lu, X.Wu, Y.Zhang, F.Li, B.Wei, J.Li, J.Wu, S.Xu, J.Wang, J.Qi, G.Shang, L.Gu.

ABSTRACT

The cyclic dinucleotide (CDN)-stimulator of interferon genes (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^CBD) in complex with CDNs at 1.76-2.6 Å resolution revealed that porcine STING^CBD, 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.