Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90242%2F24%3A00139153" target="_blank" >RIV/00216224:90242/24:00139153 - isvavai.cz</a>
Result on the web
<a href="https://www.embopress.org/doi/full/10.1038/s44318-024-00207-0" target="_blank" >https://www.embopress.org/doi/full/10.1038/s44318-024-00207-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s44318-024-00207-0" target="_blank" >10.1038/s44318-024-00207-0</a>
Alternative languages
Result language
angličtina
Original language name
Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering
Original language description
Conserved signaling cascades monitor protein-folding homeostasis to ensure proper cellular function. One of the evolutionary conserved key players is IRE1, which maintains endoplasmic reticulum (ER) homeostasis through the unfolded protein response (UPR). Upon accumulation of misfolded proteins in the ER, IRE1 forms clusters on the ER membrane to initiate UPR signaling. What regulates IRE1 cluster formation is not fully understood. Here, we show that the ER lumenal domain (LD) of human IRE1 alpha forms biomolecular condensates in vitro. IRE1 alpha LD condensates were stabilized both by binding to unfolded polypeptides as well as by tethering to model membranes, suggesting their role in assembling IRE1 alpha into signaling-competent stable clusters. Molecular dynamics simulations indicated that weak multivalent interactions drive IRE1 alpha LD clustering. Mutagenesis experiments identified disordered regions in IRE1 alpha LD to control its clustering in vitro and in cells. Importantly, dysregulated clustering of IRE1 alpha mutants led to defects in IRE1 alpha signaling. Our results revealed that disordered regions in IRE1 alpha LD control its clustering and suggest their role as a common strategy in regulating protein assembly on membranes.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
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Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Journal
ISSN
0261-4189
e-ISSN
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Volume of the periodical
43
Issue of the periodical within the volume
20
Country of publishing house
US - UNITED STATES
Number of pages
31
Pages from-to
4668-4698
UT code for WoS article
001306286100002
EID of the result in the Scopus database
2-s2.0-85203078172