Extended Data Fig. 6: SARM1^TIR is restricted in the inactive state through interactions with SARM1^ARM.

a, Structural comparison of the ARM domains in SARM1, importin-α (PDB code: 1IAL), and β-catenin (PDB code: 2BCT). ARM1-8 of SARM1^ARM, ARM3-10 of importin-α, and ARM5-12 of β-catenin are shown. The ARM motifs in the middle adopt the similar conformation and are coloured in grey. However, the conformations of ARM motifs on both ends of SARM1^ARM (ARM1, ARM7-8, and the last helix of ARM6; coloured in green) are different from those of the corresponding ARM motifs in importin-α (ARM3, ARM9-10, and the last helix of ARM8; coloured in yellow) or β-catenin (ARM5, ARM11-12, and the last helix of ARM10; coloured in pink). The last helix of ARM6 in SARM1^ARM and its corresponding helices in importin-α and β-catenin are marked out with dashed circles. Their orientations are indicated with arrows. b, Detailed interactions between the two neighbouring SARM1^ARM (green box), and between SARM1^ARM and the two closely packed SARM1^SAM (pink boxes). c, Cryo-EM densities (black mesh) of the BB-loop in the NAD⁺-bound SARM1(E642A) structure. Atomic models of αA and BB-loop are coloured in wheat and red, respectively. Relevant residues are shown with side chains. d, Cryo-EM densities of the BB-loop in SARM1 (blue mesh) and NAD⁺-bound SARM1 (green mesh) structures. The atomic model of the BB-loop in NAD⁺-bound SARM1(E642A) structure is shown as a reference. The contour levels of the maps in c and d are 6.0. e, The inactive conformation of SARM1^TIR is designated by its interactions with the two adjacent SARM1^ARM. f, The αA helix and BB-loop of different TIR domains are prone to mediate protein–protein interactions. The RRS1/RPS4 heterodimer (PDB code: 4C6T) is formed through interactions between their αA helices (in wheat), and the TLR10 homodimer (PDB code: 2J67) is assembled via the BB-loop interaction (in red). Two subunits are coloured in cyan and green, respectively.