Academic Journal
Folding kinetics of an entangled protein
| العنوان: | Folding kinetics of an entangled protein |
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| المؤلفون: | Salicari L., Baiesi M., Orlandini E., Trovato A. |
| المساهمون: | Salicari, L., Baiesi, M., Orlandini, E., Trovato, A. |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE |
| سنة النشر: | 2023 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| الوصف: | The possibility of the protein backbone adopting lasso-like entangled motifs has attracted increasing attention. After discovering the surprising abundance of natively entangled protein domain structures, it was shown that misfolded entangled subpopulations might become thermosensitive or escape the homeostasis network just after translation. To investigate the role of entanglement in shaping folding kinetics, we introduce a novel indicator and analyze simulations of a coarse-grained, structure-based model for two small single-domain proteins. The model recapitulates the well-known two-state folding mechanism of a non-entangled SH3 domain. However, despite its small size, a natively entangled antifreeze RD1 protein displays a rich refolding behavior, populating two distinct kinetic intermediates: a short-lived, entangled, near-unfolded state and a longer-lived, non-entangled, near-native state. The former directs refolding along a fast pathway, whereas the latter is a kinetic trap, consistently with known experimental evidence of two different characteristic times. Upon trapping, the natively entangled loop folds without being threaded by the N-terminal residues. After trapping, the native entangled structure emerges by either backtracking to the unfolded state or threading through the already formed but not yet entangled loop. Along the fast pathway, trapping does not occur because the native contacts at the closure of the lasso-like loop fold after those involved in the N-terminal thread, confirming previous predictions. Despite this, entanglement may appear already in unfolded configurations. Remarkably, a longer-lived, near-native intermediate, with non-native entanglement properties, recalls what was observed in cotranslational folding.Recently, a surprisingly large fraction of protein structures was shown to host topologically entangled motifs, whereby one protein chain portion is lassoed by a second portion, that loops between two residues in non-covalent contact with each other. Moreover, there is ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37956216; info:eu-repo/semantics/altIdentifier/wos/WOS:001122670200002; volume:19; issue:11; firstpage:1; lastpage:30; numberofpages:30; journal:PLOS COMPUTATIONAL BIOLOGY; https://hdl.handle.net/11577/3503972; https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011107; https://researchdata.cab.unipd.it/984/ |
| DOI: | 10.1371/journal.pcbi.1011107 |
| الاتاحة: | https://hdl.handle.net/11577/3503972 https://doi.org/10.1371/journal.pcbi.1011107 https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011107 https://researchdata.cab.unipd.it/984/ |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.EFF54B86 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pcbi.1011107 |
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