5C79

PH domain of ASAP1 in complex with diC4-PtdIns(4,5)P2

5C79 の概要

• エントリーDOI: 10.2210/pdb5c79/pdb
• 分子名称: Arf-GAP, (2R)-3-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}PROPANE-1 ,2-DIYL DIBUTANOATE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: ph domain, dic4-ptdins(4, 5)p2, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm: Q9QWY8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36444.97

構造登録者

Xia, D.,Tang, W.K. (登録日: 2015-06-24, 公開日: 2015-10-07, 最終更新日: 2024-03-06)

主引用文献

Jian, X.,Tang, W.K.,Zhai, P.,Roy, N.S.,Luo, R.,Gruschus, J.M.,Yohe, M.E.,Chen, P.W.,Li, Y.,Byrd, R.A.,Xia, D.,Randazzo, P.A.
Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1.
Structure, 23:1977-1988, 2015

PubMed Abstract: We have defined the molecular basis for association of the PH domain of the Arf GAP ASAP1 with phospholipid bilayers. Structures of the unliganded and dibutyryl PtdIns(4,5)P2-bound PH domain were solved. PtdIns(4,5)P2 made contact with both a canonical site (C site) and an atypical site (A site). We hypothesized cooperative binding of PtdIns(4,5)P2 to the C site and a nonspecific anionic phospholipid to the A site. PtdIns(4,5)P2 dependence of binding to large unilamellar vesicles and GAP activity was sigmoidal, consistent with cooperative sites. In contrast, PtdIns(4,5)P2 binding to the PH domain of PLC δ1 was hyperbolic. Mutation of amino acids in either the C or A site resulted in decreased PtdIns(4,5)P2-dependent binding to vesicles and decreased GAP activity. The results support the idea of cooperative phospholipid binding to the C and A sites of the PH domain of ASAP1. We propose that the mechanism underlies rapid switching between active and inactive ASAP1.

PubMed: 26365802
DOI: 10.1016/j.str.2015.08.008

実験手法

X-RAY DIFFRACTION (1.6 Å)