First-principles model of optimal translation factors stoichiometry
Name
elife-69222-v2.pdf
Description
Published version
Size
2.19 MB
Format
Adobe PDF
Checksum (MD5)
3b415ef2045efa66f6715973cf21ea7e
Author(s)
Lalanne, Jean-Benoît
Li, Gene-Wei
Date Issued
2021
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Lalanne, Jean-Benoît and Li, Gene-Wei. 2021. "First-principles model of optimal translation factors stoichiometry." eLife, 10.
Version
Final published version
Abstract
Enzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here, we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that predictions from maximization of ribosome usage in a parsimonious flux model constrained by proteome allocation agree with the conserved ratios of translation factors. The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.69222
