Figure 7: Structure analysis of the kinase domain of murine IRE1α.

(a) Ribbons’ representation of IRE1α kinase domains highlighting regulatory (yellow) and catalytic (red) spine alignments. All yeast structures solved to date display productive alignment of spines (right), while HAA-bound murine IRE1α structures and the dephospho-human IRE1α structure adopt non-productive alignments of the regulatory spine. PDB code and the respective ligand engaging the kinase-active site are indicated. (b) Zoom-in view of the kinase-active site of murine IRE1α superimposed on yeast IRE1 (PDB 2RIO) highlighting the displaced position of helix αC. (c) Zoom-in view of the projected back-to-back dimer interface of murine IRE1α (only one protomer shown) superimposed on the yeast IRE1 back-to-back dimer (PDB 2RIO) highlighting the physical link between helix αC and the back-to-back dimer interface. Side chains composing an essential intra-dimer salt bridge and the subdomain III glutamate side chain are shown as sticks.