An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation.

ABSTRACT: The unfolded protein response plays an evolutionarily conserved role in homeostasis, and its dysregulation often leads to human disease, including diabetes and cancer. IRE1α is a major transducer that conveys endoplasmic reticulum stress via biochemical signals, yet major gaps persist in our understanding of how the detection of stress is converted to one of several molecular outcomes. It is known that, upon sensing unfolded proteins via its endoplasmic reticulum luminal domain, IRE1α dimerizes and then oligomerizes (often visualized as clustering). Once assembled, the kinase domain trans-autophosphorylates a neighboring IRE1α, inducing a conformational change that activates the RNase effector domain. However, the full details of how the signal is transmitted are not known. Here, we descri

SUBMITTER: Ricci D 

PROVIDER: S-EPMC8203841 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature