Figure 7.

Schematic model of SARM1 activation.

In the inactive state, the ARM domain (magenta) interacts with the TIR domain (blue), separating it from the neighboring TIR domains. Upon injury, NMN interaction induces a more compact conformation of the ARM domain (grey), which leads to destabilization of the peripheral ARM domain ring, and disruption of the ARM:TIR lock. This permits the TIR domains to associate with each other, form the catalytic site, cleave NAD⁺, and trigger axon degeneration. The SAM domains are shown in lime.