دورية أكاديمية
أعرض في EDS

IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response.

التفاصيل البيبلوغرافية
العنوان: IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response.
المؤلفون: Simpson MS; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA.; Graduate School of Life Sciences, Utrecht University, Utrecht, Netherlands., De Luca H; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA., Cauthorn S; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA.; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA., Luong P; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA., Udeshi ND; Broad Institute of MIT and Harvard , Cambridge, MA, USA., Svinkina T; Broad Institute of MIT and Harvard , Cambridge, MA, USA., Schmieder SS; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Carr SA; Broad Institute of MIT and Harvard , Cambridge, MA, USA., Grey MJ; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA.; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Harvard Digestive Disease Center , Boston, MA, USA., Lencer WI; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Harvard Digestive Disease Center , Boston, MA, USA.
المصدر: The Journal of cell biology [J Cell Biol] 2024 Jul 01; Vol. 223 (7). Date of Electronic Publication: 2024 Apr 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 0375356 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-8140 (Electronic) Linking ISSN: 00219525 NLM ISO Abbreviation: J Cell Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Rockefeller University Press
مواضيع طبية MeSH: Cholera Toxin*/genetics , Cholera Toxin*/metabolism , Endoribonucleases*/genetics , Endoribonucleases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Protein Serine-Threonine Kinases*/metabolism , Unfolded Protein Response*, Endoplasmic Reticulum Stress ; Signal Transduction ; Humans ; Animals ; Mice ; Cell Line
مستخلص: IRE1α is an endoplasmic reticulum (ER) sensor that recognizes misfolded proteins to induce the unfolded protein response (UPR). We studied cholera toxin (CTx), which invades the ER and activates IRE1α in host cells, to understand how unfolded proteins are recognized. Proximity labeling colocalized the enzymatic and metastable A1 segment of CTx (CTxA1) with IRE1α in live cells, where we also found that CTx-induced IRE1α activation enhanced toxicity. In vitro, CTxA1 bound the IRE1α lumenal domain (IRE1αLD), but global unfolding was not required. Rather, the IRE1αLD recognized a seven-residue motif within an edge β-strand of CTxA1 that must locally unfold for binding. Binding mapped to a pocket on IRE1αLD normally occupied by a segment of the IRE1α C-terminal flexible loop implicated in IRE1α oligomerization. Mutation of the CTxA1 recognition motif blocked CTx-induced IRE1α activation in live cells, thus linking the binding event with IRE1α signal transduction and induction of the UPR.
(© 2024 Simpson et al.)
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معلومات مُعتمدة: K01 DK119414 United States DK NIDDK NIH HHS; P30 DK034854 United States DK NIDDK NIH HHS; R01 DK048106 United States DK NIDDK NIH HHS; R01DK048106 United States NH NIH HHS
المشرفين على المادة: 9012-63-9 (Cholera Toxin)
EC 3.1.- (Endoribonucleases)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (ERN1 protein, human)
تواريخ الأحداث: Date Created: 20240405 Date Completed: 20240408 Latest Revision: 20240408
رمز التحديث: 20240408
مُعرف محوري في PubMed: PMC10996581
DOI: 10.1083/jcb.202402062
PMID: 38578285
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-8140
DOI:10.1083/jcb.202402062