TIR Domain Proteins Are an Ancient Family of NAD⁺-Consuming Enzymes.

ABSTRACT: The Toll/interleukin-1 receptor (TIR) domain is the signature signaling domain of Toll-like receptors (TLRs) and their adaptors, serving as a scaffold for the assembly of protein complexes for innate immune signaling [1, 2]. TIR domain proteins are also expressed in plants, where they mediate disease resistance [3, 4], and in bacteria, where they have been associated with virulence [5-9]. In pursuing our work on axon degeneration [10], we made the surprising discovery that the TIR domain of SARM1 (sterile alpha and TIR motif containing 1), a TLR adaptor protein, has enzymatic activity [11]. Upon axon injury, the SARM1 TIR domain cleaves nicotinamide adenine dinucleotide (NAD⁺), destroying this essential metabolic co-factor to trigger axon destruction [11, 12]. Whereas current st

SUBMITTER: Essuman K 

PROVIDER: S-EPMC5802418 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature