Fig. 6

A model for the overall allosteric regulation of B. subtilis RNR. Without nucleotides, NrdE is a monomer, but dAMP and dATP can bind the I-site and induce a partially inhibited I-dimer. Addition of specificity effectors instead induces the monomer to form an S-dimer. When specificity effectors (including dATP) bind to the I-dimer, they induce formation of an inhibited double-helical NrdE filament composed of alternating S-dimer and I-dimer interfaces. NrdF competes for the NrdE double-helical interface, and thus NrdF binding leads to the dissociation of the NrdE double-helix into individual helical structures. NrdF binds to the helical interior of the NrdE filament, leading to an inter-subunit gap and positional confinement that prevent NrdF from accessing NrdE for turnover. Both the NrdE and NrdEF filaments are reversible by addition of ATP, which can displace dATP from the I-site and induce dissociation of the I-dimer interface. Finally, addition of NrdF to the S-dimer leads to formation of an active but asymmetric α₂β₂ tetramer in which a hinge motion between the two subunits plays an important role in activity