8IK3

Structure of Stimulator of interferon genes/ligand complex

Summary for 8IK3

• Entry DOI: 10.2210/pdb8ik3/pdb
• Related: 8IK0
• EMDB information: 35504
• Descriptor: Stimulator of interferon genes protein,Immune protein Tsi3, cGAMP (2 entities in total)
• Functional Keywords: complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 467921.61

Authors

Lu, D.F.,Shang, G.J. (deposition date: 2023-02-28, release date: 2023-05-17, Last modification date: 2024-05-01)

Primary citation

Liu, S.,Yang, B.,Hou, Y.,Cui, K.,Yang, X.,Li, X.,Chen, L.,Liu, S.,Zhang, Z.,Jia, Y.,Xie, Y.,Xue, Y.,Li, X.,Yan, B.,Wu, C.,Deng, W.,Qi, J.,Lu, D.,Gao, G.F.,Wang, P.,Shang, G.
The mechanism of STING autoinhibition and activation.
Mol.Cell, 83:1502-1518.e10, 2023

PubMed Abstract: 2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.

PubMed: 37086726
DOI: 10.1016/j.molcel.2023.03.029

Experimental method

ELECTRON MICROSCOPY (3.3 Å)