Extended Data Fig. 5: Structural analysis of the SfSTING TIR NADase domain.
From: Cryo-EM structure of an active bacterial TIR–STING filament complex
a, Surface electrostatic potential for the core dimer of SfSTING with c-di-GMP single fibre filament (left). Colouring represents surface charges (red- negative, blue- positive, white- neutral). Mainly net-neutral charged loop projections mediate filament contacts (left). Dimer electrostatics at the tetramer filament interface for SfSTING and human STING (middle and right, respectively). Conserved patches of negative and positive charge are circled. b, Alternative views of the TIR dimerization interface. The TIR CC loop βD′ and βE′ insertion in the TIR domain of SfSTING (left) with symmetry related side chains omitted for clarity. Residue D110 from the DD loop is positioned by filament contacts to insert directly into the active site of the opposing symmetry mate (right). c, Global comparison of SfSTING TIR domain monomer with prokaryotic BcThsB (Bacillus cereus MSX-D12 TIR from the Thoeris phage defense system, PDB 6LHY)20; SrMilB (Streptomyces rimofaciens hmCMP glycosylhydrolase PDB 4OHB)37; and eukaryotic TIRs VrRun1 (Vitis rotundifolia plant NLR important for resistance to grapevine disease, PDB 7RX1)21; SARM1 (Homo sapiens TIR domain containing protein important for axonal degeneration, PDB 6O0Q)19. αC denoted for orientation and because it contains the catalytic glutamate residue in each structure. While all TIR-like proteins generally share a common fold, dashed regions indicate unique and poorly conserved structural elements found within several characterized active hydrolases.
