Ire1, PERK and ATF6: other models

Competition model: Here Ire1, PERK and ATF6 are the direct sensors of ER stress sensors. Bip binds the cytosolic domains. Unfolded proteins compete for BiP. Direct association model: Here, misfolded proteins bind directly to the sensors, stimulating activation and leading to UPR responses. BiP maintains solubility of inactive Ire1, PERK and ATF6 in this model. Allosteric model: Bip binds the sensors through a different site than the unfolded protein binding site: binding misfolded proteins induces a conformational change so Bip releases the sensors. Here BiP is regarded as the direct sensor of ER stress.