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The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes

Tran NH *, Carter SD *, De Mazière A, Ashkenazi A, Klumperman J, Walter P *, Jensen GJ *. The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes. Science 374:52-57, 2021
(PMID : 34591618) (PDF)

Abstract

The signaling network of the unfolded protein response (UPR) adjusts the protein folding capacity of the endoplasmic reticulum (ER) according to need. The most conserved UPR sensor, IRE1α, spans the ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined the in-situ structure of IRE1α foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography (cryo-CLEM-ET) and complementary immuno-electron microscopy in mammalian cell lines. IRE1α foci localized to a network of narrow anastomosing ER tubes (diameter ~28 nm) with complex branching. The lumen of the tubes contained protein filaments, likely composed of arrays of IRE1α lumenal domain dimers, arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1α signaling.

  • DOI: 10.1126/science.abh2474

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