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 Pcof 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 Kcof depends on the elementary constants and , whereas the cofactor potency Pcof 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.
Korennykh et al. BMC Biology 2011 9:48 doi:10.1186/1741-7007-9-48