Common regulatory control of CTP synthase enzyme activity and filament formation

• DOI: 10.1091/mbc.e14-04-0912
• Publication Date: 2014-06-12T06:43:35Z
• Authors: Chalongrat Noree; Elena Monfort; Andrew K. Shiau; James E. Wilhelm
• Keywords: 0301 basic medicine; Protein Structure; Saccharomyces cerevisiae Proteins; 1.1 Normal biological development and functioning; Saccharomyces cerevisiae; Medical and Health Sciences; Quaternary; 03 medical and health sciences; Allosteric Regulation; Underpinning research; Catalytic Domain; Enzyme Stability; Carbon-Nitrogen Ligases; Phosphorylation; Protein Structure, Quaternary; Protein Processing; 0303 health sciences; Post-Translational; Articles; Biological Sciences; Biochemistry and cell biology; Biochemistry and Cell Biology; Generic health relevance; Protein Multimerization; Protein Processing, Post-Translational; Allosteric Site; Developmental Biology

The ability of enzymes to assemble into visible supramolecular complexes is a widespread phenomenon. Such have been hypothesized play number roles; however, little known about how the regulation enzyme activity coupled assembly/disassembly these cellular structures. CTP synthase an ideal model system for addressing this question because its regulated via multiple mechanisms and filament-forming evolutionarily conserved. Our structure-function studies in Saccharomyces cerevisiae reveal that destabilization active tetrameric form increases filament formation, suggesting filaments comprise inactive dimers. Furthermore, sites responsible feedback inhibition allosteric activation control length, implying regions can influence structure. In contrast, blocking catalysis without disrupting regulatory does not affect formation or length. Together our results argue function, but enzymatic per se, are critical controlling assembly. We predict structures general closely regulate their activity.