Stochastic protein multimerization, activity, and fitness

Kyle Hagner, Sima Setayeshgar, Michael Lynch

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Many proteins assemble into homomultimeric structures, with a number of subunits that can vary substantially among phylogenetic lineages. As protein-protein interactions require productive encounters among subunits, such variation might partially be explained by variation in cellular protein abundance. Protein abundance in turn depends on the intrinsic rates of production and decay of mRNA and protein molecules, as well as rates of cell growth and division. Using a stochastic framework for prediction of the multimeric state of a protein as a function of these processes and the free energy associated with interface-interface binding, we demonstrate agreement with a wide class of proteins using E. coli proteome data. As such, this platform, which links protein quaternary structure with biochemical rates governing gene expression, protein association and dissociation, and cell growth and division, can be extended to evolutionary models for the emergence and diversification of multimers. While it is tempting to think of multimerization as adaptive, the diversity of multimeric states raises the question of its functional role and impact on fitness. As a force driving selection, we consider the possible increase in enzymatic activity of proteins arising strictly as a consequence of interface-interface binding - namely, enhanced stability to degradation, substrate binding affinity, or catalytic rate of multimers with respect to monomers without invoking further conformational changes, as in allostery. For fixed cost of protein production, we find a benefit conferred by multimers that is dependent on context and can therefore become different in diverging lineages.

Original languageEnglish (US)
Article number062401
JournalPhysical Review E
Issue number6
StatePublished - Dec 7 2018

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Condensed Matter Physics


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