In vivo translation rates can substantially delay the cotranslational folding of the Escherichia coli cytosolic proteome

Prajwal Ciryam, Richard I. Morimoto, Michele Vendruscolo, Christopher M. Dobson, Edward P. O'Brien

Research output: Contribution to journalArticlepeer-review

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A question of fundamental importance concerning protein folding in vivo is whether the kinetics of translation or the thermodynamics of the ribosome nascent chain (RNC) complex is the major determinant of cotranslational folding behavior. This is because translation rates can reduce the probability of cotranslational folding below that associated with arrested ribosomes, whose behavior is determined by the equilibrium thermodynamics of the RNC complex. Here, we combine a chemical kinetic equation with genomic and proteomic data to predict domain folding probabilities as a function of nascent chain length for Escherichia coli cytosolic proteins synthesized on both arrested and continuously translating ribosomes. Our results indicate that, at in vivo translation rates, about one-third of the Escherichia coli cytosolic proteins exhibit cotranslational folding, with at least one domain in each of these proteins folding into its stable native structure before the full-length protein is released from the ribosome. The majority of these cotranslational folding domains are influenced by translation kinetics which reduces their probability of cotranslational folding and consequently increases the nascent chain length at which they fold into their native structures. For about 20% of all cytosolic proteins this delay in folding can exceed the length of the completely synthesized protein, causing one or more of their domains to switch from co-to posttranslational folding solely as a result of the in vivo translation rates. These kinetic effects arise from the difference in time scales of folding and amino-acid addition, and they represent a source of metastability in Escherichia coli 's proteome.

Original languageEnglish (US)
Pages (from-to)E132-E140
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 8 2013

All Science Journal Classification (ASJC) codes

  • General


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