Fig. 3: The cryo-EM structure of DSR2-TTP-NAD⁺ complex.

a Cryo-EM density maps of DSR2-TTP-NAD⁺ complex. In this drawing, the Sir2 domain tetramer is colored in cyan, while the helical repeats domain in the DSR2 dimer was colored in forest green and magenta and TTP colored in wheat. b Ribbon diagram of the DSR2-TTP-NAD⁺ complex structure, and the domains were colored as in (a). c Ribbon diagram of TTP, the secondary structures were labeled and the missing residues in the cryo-EM structure were indicated by the red dash line. d Close-up view of the NAD⁺ binding pocket in the DSR2 Sir2 domain, with the key residues for the NAD⁺ coordination shown as sticks. e The electron density map of NAD⁺ observed in the cryo-EM structure. The adenine and nicotinamide groups of NAD⁺ was labeled. f Superimposed structures of the Sir2 domains of DSR2 (NAD⁺-bound) and ThsA (ADPR-bound). The catalytical pocket composed by the H171, Y134 and N133 is indicated by the black dashed cycle. g Close-up view of the interaction surface between DSR2 and TTP. Three pairs of intermolecular anti-parallel β-sheets are formed between DSR2 and TTP. h Closed-up views of DSR2 closed cavity bound with TTP, opened cavity and superimposed structures of opened cavity to TTP bound cavity.