6PK4
cryoEM structure of the substrate-bound human CTP synthase 2 filament
Summary for 6PK4
| Entry DOI | 10.2210/pdb6pk4/pdb |
| EMDB information | 20354 |
| Descriptor | CTP synthase 2, URIDINE 5'-TRIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total) |
| Functional Keywords | enzyme, filament, protein fibril |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 267003.01 |
| Authors | Lynch, E.M.,Kollman, J.M. (deposition date: 2019-06-28, release date: 2019-12-25, Last modification date: 2024-03-20) |
| Primary citation | Lynch, E.M.,Kollman, J.M. Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments. Nat.Struct.Mol.Biol., 27:42-48, 2020 Cited by 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 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. PubMed: 31873303DOI: 10.1038/s41594-019-0352-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
Download full validation report
