Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation
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Le résumé fourni par la source
Because of vectorial protein translation, residues that interact in the native protein structure but are distantly separated in the primary sequence are unavailable simultaneously. Instead, there is a temporal delay during which the N-terminal interaction partner is unsatisfied and potentially vulnerable to non-native interactions. We introduce “Native Fold Delay” (NFD), a metric that integrates protein topology with translation kinetics to quantify such delays. We found that many proteins exhibit residues with NFDs in the range of tens of seconds. These residues, predominantly in well-structured, buried regions, often coincide with aggregation-prone regions. NFD correlates with co-translational engagement by the yeast Hsp70 chaperone Ssb, suggesting that native fold-delayed regions have a propensity to misfold. Supporting this, we show that proteins with long NFDs are more frequently co-translationally ubiquitinated and prone to aggregate upon Ssb deletion. During vectorial protein translation, native interactions are temporarily unsatisfied. Here, authors introduce “Native Fold Delay”, integrating protein topology with translation kinetics to quantify the resulting delays in co-translational folding which may result in protein aggregation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation
- Date Crossref
- 15/02/2025
- Éditeur
- Springer Science and Business Media LLC
- 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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VIB-KU Leuven Center for Brain & Disease Research pays non établi dans la noticeStructure de recherche
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KU Leuven pays non établi dans la noticeUniversité ou école supérieure
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University of Freiburg pays non établi dans la noticeUniversité ou école supérieure
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Switch Laboratory pays non établi dans la noticeStructure de recherche
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Faculty of Medicine Institute of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
VIB-KU Leuven Center for Brain & Disease Research, KU Leuven et University of Freiburg, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.