Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding

Daniel A. Nissley, Ajeet K. Sharma, Nabeel Ahmed, Ulrike A. Friedrich, Günter Kramer, Bernd Bukau, Edward P. O'Brien

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number10341
JournalNature communications
Volume7
DOIs
StatePublished - Feb 18 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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