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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: Curr Opin Neurobiol. 2019 May 6;57:171–178. doi: 10.1016/j.conb.2019.03.006

Figure 2. SARM1 structure and function.

Figure 2

A. The autoinhibitory SARM1 N terminus contains a mitochondria localization signal and ARM domains. The two SAM domains mediate multimerization. The C terminal TIR domain possesses intrinsic NAD+ cleavage activity.

B. SARM1 forms multimers. The TIR domains are inhibited in normal conditions, possibly through direct interactions with the N terminus. Axon injury activates SARM1 by releasing the auto-inhibition on the TIR domains. Activated TIRs then cleave NAD+ into Nam, ADPR and cADPR and trigger axon degeneration.