Cryo-EM structure of an active bacterial TIR-STING filament complex

Area of Science:

• Molecular Biology
• Immunology
• Structural Biology

Background:

• Stimulator of interferon genes (STING) is a crucial antiviral signaling protein conserved across species.
• STING activation relies on filament assembly triggered by cyclic dinucleotides, but the mechanism is unclear.

Purpose of the Study:

• To elucidate the molecular basis of STING filament assembly and activation in prokaryotic antiviral systems.
• To determine the structure of the active bacterial TIR-STING filament complex.

Main Methods:

• Cryogenic electron microscopy (cryo-EM) was used to determine the structure of the bacterial TIR-STING filament.
• Structural analysis focused on STING interfaces, filament assembly, and effector domain interactions.

Main Results:

• The structure reveals how STING interfaces exposed upon cyclic dinucleotide binding drive filament formation.
• Repeating dimeric STING units stack head-to-head, stabilized by cross-filament contacts.
• These contacts coordinate associated TIR NADase effector domains, leading to NAD+ hydrolysis and cell growth arrest.

Conclusions:

• The study defines the structural basis of STING filament formation in prokaryotic antiviral defense.
• STING filament assembly is a prerequisite for effector activation, revealing a stepwise mechanism.
• Conserved STING interfaces highlight potential parallels between prokaryotic and mammalian immune signaling.