Large-scale filament formation inhibits the activity of CTP synthetase.
Bottom Line: Structure-guided mutagenesis and mathematical modeling further indicate that coupling activity to polymerization promotes cooperative catalytic regulation.This previously uncharacterized regulatory mechanism is important for cellular function since a mutant that disrupts CtpS polymerization disrupts E. coli growth and metabolic regulation without reducing CTP levels.We propose that regulation by large-scale polymerization enables ultrasensitive control of enzymatic activity while storing an enzyme subpopulation in a conformationally restricted form that is readily activatable.
Affiliation: Department of Molecular Biology, Princeton University, Princeton, United States.Show MeSH
Mentions: “The cellular level of CtpS protein in E. coli grown in minimal media was 2.3 μM (Figure 1–figure supplement 2), indicating that the CtpS polymerization observed in vitro occurs within a physiologically relevant concentration regime.” This is actually right at the borderline of where in vitro activity starts to decrease. I would conclude that the proposed regulation mechanism by assembly is on the borderline of physiological significance.
Affiliation: Department of Molecular Biology, Princeton University, Princeton, United States.