8T7C

Crystal structure of human phospholipase C gamma 2

8T7C の概要

• エントリーDOI: 10.2210/pdb8t7c/pdb
• 関連するPDBエントリー: 8JQG 8JQH 8JQI
• 分子名称: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, CALCIUM ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: phospholipase c gamma 2, autoinhibition, signaling, lipid metabolism, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 136163.62

構造登録者

Chen, Y.,Choi, H.,Zhuang, N.,Hu, L.,Qian, D.,Wang, J. (登録日: 2023-06-20, 公開日: 2024-06-26, 最終更新日: 2024-12-11)

主引用文献

Shin, Y.C.,Plummer-Medeiros, A.M.,Mungenast, A.,Choi, H.W.,TenDyke, K.,Zhu, X.,Shepard, J.,Sanders, K.,Zhuang, N.,Hu, L.,Qian, D.,Song, K.,Xu, C.,Wang, J.,Poda, S.B.,Liao, M.,Chen, Y.
The crystal and cryo-EM structures of PLC gamma 2 reveal dynamic interdomain recognitions in autoinhibition.
Sci Adv, 10:eadn6037-eadn6037, 2024

PubMed Abstract: Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCγ2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCγ2. Our results provide structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.

PubMed: 39612343
DOI: 10.1126/sciadv.adn6037

実験手法

X-RAY DIFFRACTION (2.55 Å)