Open AccessModeling of C-terminal tail of human STING and its interaction with tank-binding kinase 1
Author(s) -
Rafic Yunus Al-Masri,
Hajara Audu-Bida,
Şebnem Eşsiz
Publication year - 2021
Publication title -
turkish journal of biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.323
H-Index - 38
eISSN - 1303-6092
pISSN - 1300-0152
DOI - 10.3906/biy-2108-90
Subject(s) - sting , stimulator of interferon genes , biology , tank binding kinase 1 , intracellular , protein structure , protein kinase domain , microbiology and biotechnology , binding site , kinase , biophysics , biochemistry , protein kinase a , innate immune system , gene , map kinase kinase kinase , physics , receptor , thermodynamics , mutant
Stimulator of interferon genes (STING) plays a significant role in a cell's intracellular defense against pathogens or self-DNA by inducing inflammation or apoptosis through a pathway known as cGAS-cGAMP-STING. STING uses one of its domains, the C-terminal tail (CTT) to recruit the members of the pathway. However, the structure of this domain has not been solved experimentally. STING conformation is open and more flexible when inactive. When STING gets activated by cGAMP, its conformation changes to a closed state covered by 4 beta-sheets over the binding site. This conformational change leads to its binding to Tank-binding kinase 1 (TBK1). TBK1 then phosphorylates STING aiding its entry to the cell's nucleus. In this study, we focused on the loop modeling of the CTT domain in both the active and inactive STING conformations. After the modeling step, the active and inactive STING structures were docked to one of the cGAS-cGAMP-STING pathway members, TBK1, to observe the differences of binding modes. CTT loop stayed higher in the active structure, while all the best-scored models, active or inactive, ended up around the same position with respect to TBK1. However, when the STING poses are compared with the cryo-EM image of the complex structure, the models in the active structure chain B displayed closer results to the complex structure.