Publication: Common regulatory control of CTP synthase enzyme activity and filament formation
Issued Date
2014-08-01
Resource Type
ISSN
19394586
10591524
10591524
Other identifier(s)
2-s2.0-84905234492
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Biology of the Cell. Vol.25, No.15 (2014), 2282-2290
Suggested Citation
Chalongrat Noree, Elena Monfort, Andrew K. Shiau, James E. Wilhelm Common regulatory control of CTP synthase enzyme activity and filament formation. Molecular Biology of the Cell. Vol.25, No.15 (2014), 2282-2290. doi:10.1091/mbc.E14-04-0912 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/33236
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Title
Common regulatory control of CTP synthase enzyme activity and filament formation
Abstract
The ability of enzymes to assemble into visible supramolecular complexes is a widespread phenomenon. Such complexes have been hypothesized to play a number of roles; however, little is known about how the regulation of enzyme activity is coupled to the assembly/disassembly of these cellular structures. CTP synthase is an ideal model system for addressing this question because its activity is regulated via multiple mechanisms and its filament-forming ability is evolutionarily conserved. Our structure-function studies of CTP synthase in Saccharomyces cerevisiae reveal that destabilization of the active tetrameric form of the enzyme increases filament formation, suggesting that the filaments comprise inactive CTP synthase dimers. Furthermore, the sites responsible for feedback inhibition and allosteric activation control filament length, implying that multiple regions of the enzyme can influence filament structure. In contrast, blocking catalysis without disrupting the regulatory sites of the enzyme does not affect filament formation or length. Together our results argue that the regulatory sites that control CTP synthase function, but not enzymatic activity per se, are critical for controlling filament assembly. We predict that the ability of enzymes to form supramolecular structures in general is closely coupled to the mechanisms that regulate their activity. © 2014 Noree, Monfort, et al.