6PK7

cryoEM structure of the product-bound human CTP synthase 2 filament

6PK7 の概要

• エントリーDOI: 10.2210/pdb6pk7/pdb
• EMDBエントリー: 20355
• 分子名称: CTP synthase 2, ADENOSINE-5'-DIPHOSPHATE, CYTIDINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: enzyme, filament, protein fibril
• 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: 266679.15

構造登録者

Lynch, E.M.,Kollman, J.M. (登録日: 2019-06-28, 公開日: 2019-12-25, 最終更新日: 2024-03-20)

主引用文献

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

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: 31873303
DOI: 10.1038/s41594-019-0352-5

実験手法

ELECTRON MICROSCOPY (3.1 Å)