@article{84271,
  keywords = {Models, Molecular, Kinetics, Escherichia coli, Recombinant Fusion Proteins, Mutagenesis, Site-Directed, Escherichia coli Proteins, Gene Expression, Carbon-Nitrogen Ligases, Cytidine Triphosphate, Protein Multimerization},
  author = {Rachael Barry and Anne-Florence Bitbol and Alexander Lorestani and Emeric Charles and Chris Habrian and Jesse Hansen and Hsin-Jung Li and Enoch Baldwin and Ned Wingreen and Justin Kollman and Zemer Gitai},
  title = {Large-scale filament formation inhibits the activity of CTP synthetase.},
  abstract = {<p>CTP Synthetase (CtpS) is a universally conserved and essential metabolic enzyme. While many enzymes form small oligomers, CtpS forms large-scale filamentous structures of unknown function in prokaryotes and eukaryotes. By simultaneously monitoring CtpS polymerization and enzymatic activity, we show that polymerization inhibits activity, and CtpS{\textquoteright}s product, CTP, induces assembly. To understand how assembly inhibits activity, we used electron microscopy to define the structure of CtpS polymers. This structure suggests that polymerization sterically hinders a conformational change necessary for CtpS activity. 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.</p>
},
  year = {2014},
  journal = {Elife},
  volume = {3},
  pages = {e03638},
  month = {07/2014},
  issn = {2050-084X},
  doi = {10.7554/eLife.03638},
  language = {eng},
}