+Search query
-Structure paper
| Title | Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 27, Issue 1, Page 42-48, Year 2020 |
| Publish date | Dec 23, 2019 |
Authors | Eric M Lynch / Justin M Kollman / ![]() |
| PubMed Abstract | Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by ...Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by polymerization into large-scale filaments. Here we describe an ultrasensitive form of polymerization-based regulation employed by human CTP synthase 2 (CTPS2). Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. Linking the conformational state of many CTPS2 subunits in a filament results in highly cooperative regulation, greatly exceeding the limits of cooperativity for the CTPS2 tetramer alone. The structures reveal a link between conformation and control of ammonia channeling between the enzyme's active sites, and explain differences in regulation of human CTPS isoforms. This filament-based mechanism of enhanced cooperativity demonstrates how the widespread phenomenon of enzyme polymerization can be adapted to achieve different regulatory outcomes. |
External links | Nat Struct Mol Biol / PubMed:31873303 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.1 - 3.5 Å |
| Structure data | EMDB-20354, PDB-6pk4: EMDB-20355, PDB-6pk7: |
| Chemicals | ![]() ChemComp-UTP: ![]() ChemComp-ATP: ![]() ChemComp-ADP: ![]() ChemComp-CTP: |
| Source |
|
Keywords | PROTEIN FIBRIL / Enzyme / filament |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors
External links







homo sapiens (human)
Keywords