7UN9

SfSTING with c-di-GMP double fiber

Summary for 7UN9

• Entry DOI: 10.2210/pdb7un9/pdb
• Related: 7UN8
• EMDB information: 26616 26617
• Descriptor: CD-NTase-associated protein 12, 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) (2 entities in total)
• Functional Keywords: sting, bacterial, filament, antiviral protein
• Biological source: Sphingobacterium faecium
• Total number of polymer chains: 12
• Total formula weight: 415773.31

Authors

Morehouse, B.R.,Yip, M.C.J.,Keszei, A.F.A.,McNamara-Bordewick, N.K.,Shao, S.,Kranzusch, P.J. (deposition date: 2022-04-09, release date: 2022-07-27, Last modification date: 2024-02-14)

Primary citation

Morehouse, B.R.,Yip, M.C.J.,Keszei, A.F.A.,McNamara-Bordewick, N.K.,Shao, S.,Kranzusch, P.J.
Cryo-EM structure of an active bacterial TIR-STING filament complex.
Nature, 608:803-807, 2022

PubMed Abstract: Stimulator of interferon genes (STING) is an antiviral signalling protein that is broadly conserved in both innate immunity in animals and phage defence in prokaryotes. Activation of STING requires its assembly into an oligomeric filament structure through binding of a cyclic dinucleotide, but the molecular basis of STING filament assembly and extension remains unknown. Here we use cryogenic electron microscopy to determine the structure of the active Toll/interleukin-1 receptor (TIR)-STING filament complex from a Sphingobacterium faecium cyclic-oligonucleotide-based antiphage signalling system (CBASS) defence operon. Bacterial TIR-STING filament formation is driven by STING interfaces that become exposed on high-affinity recognition of the cognate cyclic dinucleotide signal c-di-GMP. Repeating dimeric STING units stack laterally head-to-head through surface interfaces, which are also essential for human STING tetramer formation and downstream immune signalling in mammals. The active bacterial TIR-STING structure reveals further cross-filament contacts that brace the assembly and coordinate packing of the associated TIR NADase effector domains at the base of the filament to drive NAD hydrolysis. STING interface and cross-filament contacts are essential for cell growth arrest in vivo and reveal a stepwise mechanism of activation whereby STING filament assembly is required for subsequent effector activation. Our results define the structural basis of STING filament formation in prokaryotic antiviral signalling.

PubMed: 35859168
DOI: 10.1038/s41586-022-04999-1

Experimental method

ELECTRON MICROSCOPY (3.3 Å)