4EF4

Crystal structure of STING CTD complex with c-di-GMP

Summary for 4EF4

• Entry DOI: 10.2210/pdb4ef4/pdb
• Related: 4EF5
• Descriptor: Transmembrane protein 173, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one), CALCIUM ION, ... (4 entities in total)
• Functional Keywords: sting/mita/eris/mpys/tmem173, innate immune system, type i interferon, dimerization, c-di-gmp, 5 helices and 5 strands in single domain, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q86WV6
• Total number of polymer chains: 2
• Total formula weight: 60467.49

Authors

Ouyang, S.,Ru, H.,Shaw, N.,Jiang, Y.,Niu, F.,Zhu, Y.,Qiu, W.,Li, Y.,Liu, Z.-J. (deposition date: 2012-03-29, release date: 2012-05-16, Last modification date: 2024-03-20)

Primary citation

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.
Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding
Immunity, 36:1073-1086, 2012

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.

PubMed: 22579474
DOI: 10.1016/j.immuni.2012.03.019

Experimental method

X-RAY DIFFRACTION (2.147 Å)