The stress-sensing domain of activated IRE1 alpha forms helical filaments in narrow ER membrane tubes

Ngoc-Han Tran; Stephen D Carter; Ann De Mazière; Avi Ashkenazi; Judith Klumperman; Peter Walter; Grant J Jensen

doi:10.1126/science.abh2474

The stress-sensing domain of activated IRE1 alpha forms helical filaments in narrow ER membrane tubes

Ngoc-Han Tran, Stephen D Carter, Ann De Mazière, Avi Ashkenazi, Judith Klumperman, Peter Walter, Grant J Jensen

Research output: Contribution to journal › Article › Academic › peer-review

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, IRE1a, spans the ER membrane and activates through oligomerization. IRE1a oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1a foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography and complementary immuno-electron microscopy in mammalian cell lines. IRE1a foci localized to a network of narrow anastomosing ER tubes (diameter, ∼28 nm) with complex branching. The lumen of the tubes contained protein filaments, which were likely composed of arrays of IRE1a lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1a signaling.

Original language	English
Pages (from-to)	52-57
Number of pages	6
Journal	Science
Volume	374
Issue number	6563
DOIs	https://doi.org/10.1126/science.abh2474
Publication status	Published - 1 Oct 2021

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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, IRE1a, spans the ER membrane and activates through oligomerization. IRE1a oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1a foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography and complementary immuno-electron microscopy in mammalian cell lines. IRE1a foci localized to a network of narrow anastomosing ER tubes (diameter, ∼28 nm) with complex branching. The lumen of the tubes contained protein filaments, which were likely composed of arrays of IRE1a lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1a signaling.",

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AU - Tran, Ngoc-Han

AU - Carter, Stephen D

AU - De Mazière, Ann

AU - Ashkenazi, Avi

AU - Klumperman, Judith

AU - Walter, Peter

AU - Jensen, Grant J

PY - 2021/10/1

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AB - 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, IRE1a, spans the ER membrane and activates through oligomerization. IRE1a oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1a foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography and complementary immuno-electron microscopy in mammalian cell lines. IRE1a foci localized to a network of narrow anastomosing ER tubes (diameter, ∼28 nm) with complex branching. The lumen of the tubes contained protein filaments, which were likely composed of arrays of IRE1a lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1a signaling.

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The stress-sensing domain of activated IRE1 alpha forms helical filaments in narrow ER membrane tubes

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