Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding
The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain’s co-translational folding curve du...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
18 Feb 2016
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| In: |
Nature Communications
Year: 2016, Jahrgang: 7, Pages: 10341 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms10341 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms10341 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms10341 
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| Verfasserangaben: | Daniel A. Nissley, Ajeet K. Sharma, Nabeel Ahmed, Ulrike A. Friedrich, Günter Kramer, Bernd Bukau & Edward P. O’Brien |
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| 520 | |a The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain’s co-translational folding curve during synthesis using only the domain’s bulk folding and unfolding rates and codon translation rates. We show that this model accurately predicts the course of co-translational folding measured in vivo for four different protein molecules. We then make predictions for a number of different proteins in yeast and find that synonymous codon substitutions, which change translation-elongation rates, can switch some protein domains from folding post-translationally to folding co-translationally—a result consistent with previous experimental studies. Our approach explains essential features of co-translational folding curves and predicts how varying the translation rate at different codon positions along a transcript’s coding sequence affects this self-assembly process. | ||
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