Figure 6

Model of cofactor action during Ire1 oligomerization and activation. (a) Two-step model for oligomerization and activation of apo-Ire1. (b) Three-step model for cofactor-stimulated Ire1 activation involving equilibrium of two distinct cofactor-bound Ire1 species. The macroscopic parameter P_cof depends on the ratio of cofactor-bound Ire1 populations in "inactive" conformation (marked as "O", which designates the αC-helix in the "out" position seen in the inactive conformation of CDK2) and in "active" conformation required for the oligomer assembly (marked as "I", which designates the αC-helix in the "in" position seen in the active conformation of CDK2). The macroscopic apparent cofactor binding constant K_cof depends on the elementary constants and , whereas the cofactor potency P_cof depends on the and (Additional file 1, Supplementary Analysis 1). (c) Schematic free-energy diagram for the cofactor-independent and the cofactor-facilitated Ire1 oligomerization that corresponds to the schemes shown in (a) and (b). The shift in the oligomerization equilibrium arises from the stabilization of monomer "I" by cofactors.