TY - JOUR
T1 - Stochastic protein multimerization, activity, and fitness
AU - Hagner, Kyle
AU - Setayeshgar, Sima
AU - Lynch, Michael
N1 - Publisher Copyright:
© 2018 American Physical Society.
PY - 2018/12/7
Y1 - 2018/12/7
N2 - 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.
AB - 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.
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U2 - 10.1103/PhysRevE.98.062401
DO - 10.1103/PhysRevE.98.062401
M3 - Article
C2 - 31214661
AN - SCOPUS:85058337465
SN - 2470-0045
VL - 98
JO - Physical Review E
JF - Physical Review E
IS - 6
M1 - 062401
ER -