[PDF][PDF] Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding

S Ouyang, X Song, Y Wang, H Ru, N Shaw, Y Jiang… - Immunity, 2012 - cell.com
S Ouyang, X Song, Y Wang, H Ru, N Shaw, Y Jiang, F Niu, Y Zhu, W Qiu, K Parvatiyar, Y Li…
Immunity, 2012cell.com
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 …
Summary
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.
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