Fig. 5: Model of NorQD action.
From: NorQD AAA+ complex drives metal insertion by a twisting mechanism
a Proposed mechanism for NorQD facilitated iron insertion into cNOR. 1. NorQ alone forms a flat, hexameric ring, shown in blue. The AlphaFold 3 model of NorD, with the finger in red, the VWA domain in hot pink, linker region in lilac and the N-terminal domain in purple. 2. NorQ and NorD form a complex, inducing a spiral staircase configuration in NorQ. This conformation resembles state 1 of JtNorQWBNorD. 3. The NorQD complex binds to membrane-bound cNOR (outlined schematically in grey) via NorD, probably involving a) the VWA MIDAS site or linker and two conserved cNOR acidic surface residues and b) at least one additional site on the N-terminal domain and/or the linker. 4. ATP hydrolysis in a hand-over-hand mechanism by NorQ causes rotation of the VWA domain, including the finger domain as seen in state 2 of JtNorQWBNorD. This causes conformational changes in the linker, which is stretched out, hypothetically resulting in conformational changes in cNOR. 5. ATP hydrolysis continues, and the linker is further stretched out, as seen in state 3 of JtNorQWBNorD, which also could lead to further conformational changes in cNOR. This would allow for iron to be inserted into the active site of cNOR. 6. NorQD unbinds upon conformational changes in the linker and VWA domains, state 4 of JtNorQWBNorD. The N-terminal domain of NorD must detach from the ring for a new round of iron insertion. b Close-up view onto membrane-facing surface of NorQD complex of steps 3 to 6 as described above with indication of distance between linker attachment points in green. The location of the MIDAS motif is indicated by a black oval.
