8W2H

Human liver phosphofructokinase-1 in the T-state conformation

8W2H の概要

• エントリーDOI: 10.2210/pdb8w2h/pdb
• EMDBエントリー: 43748
• 分子名称: ATP-dependent 6-phosphofructokinase, liver type, 1,6-di-O-phosphono-beta-D-fructofuranose, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: pfk, glycolysis, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 348025.36

構造登録者

Lynch, E.M.,Kollman, J.M.,Webb, B.A. (登録日: 2024-02-20, 公開日: 2024-09-11, 最終更新日: 2024-09-25)

主引用文献

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

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: 39183237
DOI: 10.1038/s41467-024-51808-6

実験手法

ELECTRON MICROSCOPY (2.6 Å)