ER stress signalling by the UPR activator IRE1 and its regulation by BiP

点击翻译按钮获取中文摘要

The Endoplasmic Reticulum (ER) is a major compartment within the human cell that is important for ensuring proteinsattain their correct shape, particularly secretory proteins such as antibodies and hormones. The sudden requirement toproduce large quantities of secretory proteins can overwhelm the ER's capacity to correctly maintain protein structure,which can result in neurological diseases andcancer. A rectifying signal is initiated that bolsters the ER's capacity to maintain protein homeostasis. The stress receptorIRE1 is a critical component of this process. However, the molecular details of IRE1 signal activation are not clearlyunderstood.Using purified proteins and a biochemical, cellular and structural based approach, we aim to understand how IRE1 is activated inresponse to an increase in misfolded protein within the ER that leads to UPR Furthermore, we aim to visualise the 3D shape of IRE1 facilitating further insights into signal activation. Thus, the proposalwill generate novel insights into IRE1 mechanism towards providing a better understanding of how to target IRE1 signallingin disease.