4HND

Crystal structure of the catalytic domain of Selenomethionine substituted human PI4KIIalpha in complex with ADP

4HND の概要

• エントリーDOI: 10.2210/pdb4hnd/pdb
• 関連するPDBエントリー: 4HNE
• 分子名称: Phosphatidylinositol 4-kinase type 2-alpha, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• 機能のキーワード: pi3k/pi4k kinase, lipid kinase, atp binding, palmitoylation, membrane anchoring, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus, trans-Golgi network membrane ; Lipid-anchor : Q9BTU6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88785.53

構造登録者

Zhou, Q.,Zhai, Y.,Zhang, K.,Chen, C.,Sun, F. (登録日: 2012-10-19, 公開日: 2014-04-09, 最終更新日: 2024-11-06)

主引用文献

Zhou, Q.,Li, J.,Yu, H.,Zhai, Y.,Gao, Z.,Liu, Y.,Pang, X.,Zhang, L.,Schulten, K.,Sun, F.,Chen, C.
Molecular insights into the membrane-associated phosphatidylinositol 4-kinase II alpha.
Nat Commun, 5:3552-3552, 2014

PubMed Abstract: Phosphatidylinositol 4-kinase IIα (PI4KIIα), a membrane-associated PI kinase, plays a central role in cell signalling and trafficking. Its kinase activity critically depends on palmitoylation of its cysteine-rich motif (-CCPCC-) and is modulated by the membrane environment. Lack of atomic structure impairs our understanding of the mechanism regulating kinase activity. Here we present the crystal structure of human PI4KIIα in ADP-bound form. The structure identifies the nucleotide-binding pocket that differs notably from that found in PI3Ks. Two structural insertions, a palmitoylation insertion and an RK-rich insertion, endow PI4KIIα with the 'integral' membrane-binding feature. Molecular dynamics simulations, biochemical and mutagenesis studies reveal that the palmitoylation insertion, containing an amphipathic helix, contributes to the PI-binding pocket and anchors PI4KIIα to the membrane, suggesting that fluctuation of the palmitoylation insertion affects PI4KIIα's activity. We conclude from our results that PI4KIIα's activity is regulated indirectly through changes in the membrane environment.

PubMed: 24675427
DOI: 10.1038/ncomms4552

実験手法

X-RAY DIFFRACTION (3.2 Å)