Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1

• Published in: Frontiers in molecular biosciences Vol. 6; p. 11
• Main Authors: Adams, Christopher J., Kopp, Megan C., Larburu, Natacha, Nowak, Piotr R., Ali, Maruf M. U.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12.03.2019
• Subjects: BiP; crystal structures; ER stress; Hsp70; IRE1 inositol-requiring enzyme 1; Molecular Biosciences; unfolded protein response (UPR); BiP; ER stress; Hsp70; IRE1 inositol-requiring enzyme 1; crystal structures; unfolded protein response (UPR)
• ISSN: 2296-889X; 2296-889X
• DOI: 10.3389/fmolb.2019.00011

The endoplasmic reticulum (ER) is an important site for protein folding and maturation in eukaryotes. The cellular requirement to synthesize proteins within the ER is matched by its folding capacity. However, the physiological demands or aberrations in folding may result in an imbalance which can lead to the accumulation of misfolded protein, also known as "ER stress." The unfolded protein response (UPR) is a cell-signaling system that readjusts ER folding capacity to restore protein homeostasis. The key UPR signal activator, IRE1, responds to stress by propagating the UPR signal from the ER to the cytosol. Here, we discuss the structural and molecular basis of IRE1 stress signaling, with particular focus on novel mechanistic advances. We draw a comparison between the recently proposed allosteric model for UPR induction and the role of Hsp70 during polypeptide import to the mitochondrial matrix.