Protein scaffolds can enhance the bistability of multisite phosphorylation systems.
The phosphorylation of a substrate at multiple sites is a common protein modification that can give rise to important structural and electrostatic changes. Scaffold proteins can enhance protein phosphorylation by facilitating an interaction between a protein kinase enzyme and its target substrate. In this work we consider a simple mathematical model of a scaffold protein and show that under specific conditions, the presence of the scaffold can substantially raise the likelihood that the resulting system will exhibit bistable behavior. This phenomenon is especially pronounced when the enzymatic reactions have sufficiently large K(M), compared to the concentration of the target substrate. We also find for a closely related model that bistable systems tend to have a specific kinetic conformation. Using deficiency theory and other methods, we provide a number of necessary conditions for bistability, such as the presence of multiple phosphorylation sites and the dependence of the scaffold binding/unbinding rates on the number of phosphorylated sites.
Department of Mathematics, Center for Mathematical and Complex Biological Systems, Center for Complex Biological Systems, University of California, Irvine, California, USA.
Carlo
C
Chan
Xinfeng
X
Liu
Liming
L
Wang
Lee
L
Bardwell
Qing
Q
Nie
Germán
G
Enciso
D001665:Binding Sites; D019295:Computational Biology; D003198:Computer Simulation; D007700:Kinetics; D016014:Linear Models; D008954:Models, Biological; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D011506:Proteins; D011494:Protein Kinases