Tran, N.-H., Carter, S. D. , De Mazière, A., Ashkenazi, A., Klumperman, J., Walter, P. and Jensen, G. J. (2021) The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes. Science, 374(6563), pp. 52-57. (doi: 10.1126/science.abh2474) (PMID:34591618)
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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, 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 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, which were likely composed of arrays of IRE1α lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1α signaling.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Carter, Dr Stephen |
| Creator Roles: | |
| Authors: | Tran, N.-H., Carter, S. D., De Mazière, A., Ashkenazi, A., Klumperman, J., Walter, P., and Jensen, G. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Science |
| Publisher: | American Association for the Advancement of Science |
| ISSN: | 0036-8075 |
| ISSN (Online): | 1095-9203 |
| Published Online: | 30 September 2021 |
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