Proteome folding kinetics is limited by protein halflife

Taisong Zou, Nickolas Williams, Sefika Ozkan, Kingshuk Ghosh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution - using the native topology - for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distributions with average folding times of 100 milliseconds and 170 milliseconds, respectively. The topology-based folding time distribution is well described by a diffusion-drift mutation model on a flat-fitness landscape in free energy barrier between two boundaries: i) the lowest barrier height determined by the upper limit of folding speed and ii) the highest barrier height governed by the lower speed limit of folding. While the fastest time scale of the distribution is near the experimentally measured speed limit of 1 microsecond (typical of barrier-less folders), we find the slowest folding time to be around seconds (≈8 seconds for Yeast distribution), approximately an order of magnitude less than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This separation of timescale implies even the fastest degrading protein will have moderately high (96%) probability of folding before degradation. The overall agreement with the flat-fitness landscape model further hints that proteome folding times did not undergo additional major selection pressures - to make proteins fold faster - other than the primary requirement to "sufficiently beat the clock" against its lifetime. Direct comparison between the predicted folding time and experimentally measured halflife further shows 99% of the proteome have a folding time less than their corresponding lifetime. These two findings together suggest that proteome folding kinetics may be bounded by protein halflife.

Original languageEnglish (US)
Article numbere112701
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 13 2014

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Proteome
proteome
half life
Half-Life
kinetics
Kinetics
Yeast
Yeasts
Proteins
yeasts
proteins
topology
Escherichia coli
Topology
Energy barriers
Free energy
Clocks
mutation
Pressure
Degradation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Proteome folding kinetics is limited by protein halflife. / Zou, Taisong; Williams, Nickolas; Ozkan, Sefika; Ghosh, Kingshuk.

In: PLoS One, Vol. 9, No. 11, e112701, 13.11.2014.

Research output: Contribution to journalArticle

Zou, Taisong ; Williams, Nickolas ; Ozkan, Sefika ; Ghosh, Kingshuk. / Proteome folding kinetics is limited by protein halflife. In: PLoS One. 2014 ; Vol. 9, No. 11.
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