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. Author manuscript; available in PMC: 2024 Aug 19.
Published in final edited form as: Nature. 2023 Jul 26;621(7977):154–161. doi: 10.1038/s41586-023-06456-z

Fig. 3 |. Central TIR cluster.

Fig. 3 |

a, Ribbon diagram of the TIR tetramer with each TIR colored individually. The TIRs are related by a 21-screw axis.

b, Schematic diagram illustrating the stacking and interfaces of TIRs.

c, Catalytic interface between TIRIA and TIRIIA mediated by BB loop of TIRIIA and 𝛂E and DE loop of TIRIA.

d, Tetramerization interface between TIRIA and TIRIB formed by 𝛂B and 𝛂C of TIRIA and DE loop of TIRIB.

e, Interactions of TIRIA with TIRIB and TIRIIB via the same tetramerization interface.

f, Lack of NAD+ hydrolase activity in mutants with compromised TIR-TIR interactions. V113R and V113R/D106R/D111R disrupt TIR tetramerization while G42R/D44R disrupts TIR dimerization. TIR domain alone also lacked catalytic activity. Data are mean ± SD from more than 3 replicates as indicated (Wild type, n=6; G42R/D44R, n=3; V113R, n=5; V113R/D106R/D111R, n=3; TIR, n=5).

g, An expanded view of the catalytic interface with NAD+ shown as sticks.

h, Mutations of residues coordinating NAD+ impaired NAD+ hydrolysis. Data are mean ± SD from more than 3 replicates as indicated (Wild type, n=6; F45A/W46A, n=3; N116W, n=6; Y105A, n=4).