8W2H
Human liver phosphofructokinase-1 in the T-state conformation
Summary for 8W2H
| Entry DOI | 10.2210/pdb8w2h/pdb |
| EMDB information | 43748 |
| Descriptor | ATP-dependent 6-phosphofructokinase, liver type, 1,6-di-O-phosphono-beta-D-fructofuranose, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | pfk, glycolysis, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 348025.36 |
| Authors | Lynch, E.M.,Kollman, J.M.,Webb, B.A. (deposition date: 2024-02-20, release date: 2024-09-11, Last modification date: 2024-09-25) |
| Primary citation | Lynch, E.M.,Hansen, H.,Salay, L.,Cooper, M.,Timr, S.,Kollman, J.M.,Webb, B.A. Structural basis for allosteric regulation of human phosphofructokinase-1. Nat Commun, 15:7323-7323, 2024 Cited by PubMed Abstract: Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery; molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells. PubMed: 39183237DOI: 10.1038/s41467-024-51808-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.6 Å) |
Structure validation
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