4Q9V

Crystal structure of TIPE3

4Q9V の概要

• エントリーDOI: 10.2210/pdb4q9v/pdb
• 関連するPDBエントリー: 3F4M
• 分子名称: Tumor necrosis factor alpha-induced protein 8-like protein 3, CHLORIDE ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: helix, lipid transfer protein, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44224.06

構造登録者

Wu, J.,Zhang, X.,Chen, Y.H.,Shi, Y. (登録日: 2014-05-02, 公開日: 2014-10-22, 最終更新日: 2023-11-08)

主引用文献

Fayngerts, S.A.,Wu, J.,Oxley, C.L.,Liu, X.,Vourekas, A.,Cathopoulis, T.,Wang, Z.,Cui, J.,Liu, S.,Sun, H.,Lemmon, M.A.,Zhang, L.,Shi, Y.,Chen, Y.H.
TIPE3 Is the Transfer Protein of Lipid Second Messengers that Promote Cancer.
Cancer Cell, 26:465-478, 2014

PubMed Abstract: More than half of human cancers have aberrantly upregulated phosphoinositide signals; yet how phospholipid signals are controlled during tumorigenesis is not fully understood. We report here that TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. High-resolution crystal structure of TIPE3 shows a large hydrophobic cavity that is occupied by a phospholipid-like molecule. TIPE3 preferentially captures and shuttles two lipid second messengers, i.e., phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, and increases their levels in the plasma membrane. Notably, human cancers have markedly upregulated TIPE3 expression. Knocking out TIPE3 diminishes tumorigenesis, whereas enforced TIPE3 expression enhances it in vivo. Thus, the function and metabolism of phosphoinositide second messengers are controlled by a specific transfer protein during tumorigenesis.

PubMed: 25242044
DOI: 10.1016/j.ccr.2014.07.025

実験手法

X-RAY DIFFRACTION (2.3 Å)