Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP

• Published in: Nature structural & molecular biology Vol. 19; no. 7; pp. 725 - 727
• Main Authors: Shang, Guijun, Zhu, Deyu, Li, Ning, Zhang, Junbing, Zhu, Chunyuan, Lu, Defen, Liu, Cuilan, Yu, Qian, Zhao, Yanyu, Xu, Sujuan, Gu, Lichuan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2012; Nature Publishing Group
• Subjects: 631/250/255; 631/250/516; 631/535; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; brief-communication; Cellular proteins; Crystal structure; Cyclic GMP - analogs & derivatives; Deoxyribonucleic acid; DNA; Genetic aspects; Humans; Immunology; Life Sciences; Membrane Biology; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Models, Molecular; Protein binding; Protein Conformation; Protein Structure; Proteins; Sensors; Structure; China
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.2332

STING is an important component of the innate immune system involved in the direct response to the bacterial second messenger c-di-GMP. The structures of human STING in the presence and absence of c-di-GMP show how recognition of c-di-GMP is achieved by dimeric STING, providing a basis for future studies investigating signal transduction mechanisms. STING functions as both an adaptor protein signaling cytoplasmic double-stranded DNA and a direct immunosensor of cyclic diguanylate monophosphate (c-di-GMP). The crystal structures of the C-terminal domain of human STING (STING CTD ) and its complex with c-di-GMP reveal how STING recognizes c-di-GMP. In response to c-di-GMP binding, two surface loops, which serve as a gate and latch of the cleft formed by the dimeric STING CTD , undergo rearrangements to interact with the ligand.