Mapping Dynamic Protein Clustering with AIEgen‐Active Chemigenetic Probe
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Le résumé fourni par la source
Abstract Protein clustering/disassembling is a fundamental process in biomolecular condensates, playing a crucial role in cell fate decision and cellular homeostasis. However, the inherent features of protein clustering, especially for its reversible behavior and subtle microenvironment variation, present significant hurdles in probe chemistry for tracking protein clustering dynamics. Herein, we report a bilateral‐tailored chemigenetic probe, in which an “amphiphilic” aggregate‐induced emission luminogen (AIEgen) QMSO3Cl is covalently conjugated to a protein tag that is genetically fused to protein‐of‐interest (POI). Prior to target POI, the “amphiphilic” AIE‐active QMSO3Cl achieves a completely dark state in both aqueous biological environment and lipophilic organelles, thereby ensuring an ultra‐low intrinsic background interference. Upon reaching POI, the combination of synthetic molecule and genetically encoded protein allows for protein clustering‐dependent ultra‐sensitive response, with a substantial lighting‐up fluorescence (67.5‐fold) as protein transitions from disassembling to clustering state. Such ultra‐high signal‐to‐noise ratio enables to monitor the dynamic and fate of inositol requiring enzyme 1 (IRE1) clustering/disassembling under both acute and chronic endoplasmic reticulum (ER) stress in living cells. For the first time, we have demonstrated the use of chemigenetic probe to reveal therapy‐induced ER stress and screen drugs in a three‐dimensional scenario: microviscosity change, clustering dynamic, and cluster morphology. This chemigenetic probe design strategy would greatly facilitate the advancement of mapping protein dynamics in cell homeostasis and medicine research.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Mapping Dynamic Protein Clustering with AIEgen‐Active Chemigenetic Probe
- Date Crossref
- 29/01/2025
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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East China University of Science and Technology State Key Laboratory of Bioreactor Engineering pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
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Peking Union Medical College Hospital Stem Cell and Regenerative Medicine Lab pays non établi dans la noticeÉtablissement de santé
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Jiangnan University Key Laboratory of Carbohydrate Vaccines and Drugs in Jiangsu Province pays non établi dans la noticeUniversité ou école supérieure
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School of Chemistry and Molecular Engineering East China Univ Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering pays non établi dans la noticeUniversité ou école supérieure
State Key Laboratory of Bioreactor Engineering — East China University of Science and Technology, Chinese Academy of Medical Sciences & Peking Union Medical College et Stem Cell and Regenerative Medicine Lab — Peking Union Medical College Hospital, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.