Download MendeleyStructural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding
Ouyang, S., Song, X., Wang, Y., Ru, H., Shaw, N., Jiang, Y., Niu, F., Zhu, Y., Qiu, W., Parvatiyar, K., Li, Y., Zhang, R., Cheng, G., Liu, Z.J.(2012) Immunity 36: 1073-1086
- PubMed: 22579474
- DOI: https://doi.org/10.1016/j.immuni.2012.03.019
- Primary Citation of Related Structures:
4EF4, 4EF5 - PubMed Abstract:
STING is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway. It contains an N-terminal transmembrane region and a cytosolic C-terminal domain (CTD). Here, we describe crystal structures of STING CTD alone and complexed with c-di-GMP in a unique binding mode. The strictly conserved aa 153-173 region was shown to be cytosolic and participated in dimerization via hydrophobic interactions. The STING CTD functions as a dimer and the dimerization was independent of posttranslational modifications. Binding of c-di-GMP enhanced interaction of a shorter construct of STING CTD (residues 139-344) with TBK1. This suggests an extra TBK1 binding site, other than serine 358. This study provides a glimpse into the unique architecture of STING and sheds light on the mechanism of c-di-GMP-mediated TBK1 signaling.
Organizational Affiliation:
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
