Fig. 6: Tube-mediated conformational changes activate NADase activity of DSR2.
From: Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion
A Top and side views of cryo-EM density maps of the apo DSR2 tetramer in the inactive state (top), the DSR2-DSAD1 complex in the inhibited state (middle), and the DSR2H171A-Tube in the active state (bottom). Four DSR2s are colored in pale green, forest, light blue and teal, respectively. DSAD1 is colored in purple. Tube is colored in yellow. The conformation of the active state of DSR2H171A-Tube was significantly more compact than the inactive and inhibited states. B Left, structural alignment of the protomers of apo DSR2 (light blue) and the active DSR2-Tube complex (brown for active DSR2 and yellow for Tube). Upon binding to the Tube protein, CTD circular solenoid lid of active DSR2 tilts ~30° to bind tightly to the Tube protein, while the SIR2 domain tilts ~13°. Right, structural alignment of the protomers of apo DSR2 (light blue) and DSR2-DSAD1 complex (purple for inhibited DSR2 and violet for DSAD1). C The interface between SIR2(a) and MD(b) from the adjacent DSR2(b). D The DSR2loop143-148, DSR2I463G/Y471G, DSR2N521G/F522G/M531G/P532G and DSR2linker mutations at the SIR2(a)-MD(b) interface resulted in alterations in NAD+ cleavage. Wild-type DSR2 was used as control. Data are presented as means ± SD (n = 5 independent experiments).
