7K2V

PIKfyve/Fig4/Vac14 complex centered on PIKfyve - map2

7K2V の概要

• エントリーDOI: 10.2210/pdb7k2v/pdb
• EMDBエントリー: 22631 22634 22647
• 分子名称: 1-phosphatidylinositol 3-phosphate 5-kinase (2 entities in total)
• 機能のキーワード: lipid kinase, lipid phosphatase, protein complex, lipid binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81876.01

構造登録者

Lees, J.A.,Reinisch, K.M.,Li, P. (登録日: 2020-09-09, 公開日: 2020-10-21, 最終更新日: 2024-03-06)

主引用文献

Lees, J.A.,Li, P.,Kumar, N.,Weisman, L.S.,Reinisch, K.M.
Insights into Lysosomal PI(3,5)P 2 Homeostasis from a Structural-Biochemical Analysis of the PIKfyve Lipid Kinase Complex.
Mol.Cell, 80:736-743.e4, 2020

PubMed Abstract: The phosphoinositide PI(3,5)P, generated exclusively by the PIKfyve lipid kinase complex, is key for lysosomal biology. Here, we explore how PI(3,5)P levels within cells are regulated. We find the PIKfyve complex comprises five copies of the scaffolding protein Vac14 and one copy each of the lipid kinase PIKfyve, generating PI(3,5)P from PI3P and the lipid phosphatase Fig4, reversing the reaction. Fig4 is active as a lipid phosphatase in the ternary complex, whereas PIKfyve within the complex cannot access membrane-incorporated phosphoinositides due to steric constraints. We find further that the phosphoinositide-directed activities of both PIKfyve and Fig4 are regulated by protein-directed activities within the complex. PIKfyve autophosphorylation represses its lipid kinase activity and stimulates Fig4 lipid phosphatase activity. Further, Fig4 is also a protein phosphatase acting on PIKfyve to stimulate its lipid kinase activity, explaining why catalytically active Fig4 is required for maximal PI(3,5)P production by PIKfyve in vivo.

PubMed: 33098764
DOI: 10.1016/j.molcel.2020.10.003

実験手法

ELECTRON MICROSCOPY (6.6 Å)