Extended Data Fig. 7: Model of the mechanochemical cycle of the DEAH/RHA helicase DHX36.

The domain motions are based on the superpositions in Extended Data Fig. 6. The orange, green, yellow, and blue blocks represent the RecA1 domain, RecA2 domain, C-terminal domain, and N-terminal extension, respectively. The purple wedge represents the OB domain. Bold dotted lines represent likely intrinsically disordered protein motifs that fold upon G-quadruplex binding. a, b, In the absence of a G-quadruplex nucleic acid substrate, DHX36 cycles between an apo (or structurally indistinguishable ATP-bound) state and a post-hydrolysis state. c, d, DHX36 binds the G-quadruplex substrate and pulls on it in the 3′-direction through concerted and opposite rotations of the RecA2 and C-terminal domains. Oscillation of the RecA2 and C-terminal domains is likely to be responsible for the ATP-independent repetitive unfolding activity detected by smFRET²² (Extended Data Fig. 2 and Fig. 4). d, e, Binding of ATP induces domain closure. f, g, ATP hydrolysis yields a post-hydrolysis state that is incompatible with nucleic acid binding. ADP dissociates, and DHX36 is reset back to its apo state (c). In addition to the rearrangement of motif Va¹⁷, ATP hydrolysis is stimulated by nucleic acid binding, probably because nucleic acid binding results in the opening of the helicase core. Diffusion into the NTP binding pocket is thus increased. The model in e is based on the superposition in Extended Data Fig. 6b. The model in f is based on the superposition in Extended Data Fig. 6c. The model in f is based on the superposition in Extended Data Fig. 6c. The model in g is based on the superposition in Extended Data Fig. 6d.