4MXP

Structural Basis for PI(4)P-Specific Membrane Recruitment of the Legionella pneumophila Effector DrrA/SidM

4MXP の概要

• エントリーDOI: 10.2210/pdb4mxp/pdb
• 分子名称: Defects in Rab1 recruitment protein A, (2R)-3-{[(R)-hydroxy{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-tetrahydroxy-4-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dibutanoate, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: protein-lipid complex, guanine nucleotide exchange factor, rab1 binding, pi(4)p-binding protein
• 由来する生物種: Legionella pneumophila subsp. pneumophila
• 細胞内の位置: Secreted: Q5ZSQ3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37691.56

構造登録者

Del Campo, C.M.,Mishra, A.K.,Wang, Y.H.,Roy, C.R.,Janmey, P.A.,Lambright, D.G. (登録日: 2013-09-26, 公開日: 2014-03-19, 最終更新日: 2023-09-20)

主引用文献

Del Campo, C.M.,Mishra, A.K.,Wang, Y.H.,Roy, C.R.,Janmey, P.A.,Lambright, D.G.
Structural Basis for PI(4)P-Specific Membrane Recruitment of the Legionella pneumophila Effector DrrA/SidM.
Structure, 22:397-408, 2014

PubMed Abstract: Recruitment of the Legionella pneumophila effector DrrA to the Legionella-containing vacuole, where it activates and AMPylates Rab1, is mediated by a P4M domain that binds phosphatidylinositol 4-phosphate [PI(4)P] with high affinity and specificity. Despite the importance of PI(4)P in Golgi trafficking and its manipulation by pathogens, the structural bases for PI(4)P-dependent membrane recruitment remain poorly defined. Here, we determined the crystal structure of a DrrA fragment including the P4M domain in complex with dibutyl PI(4)P and investigated the determinants of phosphoinositide recognition and membrane targeting. Headgroup recognition involves an elaborate network of direct and water-mediated interactions with basic and polar residues in the context of a deep, constrictive binding pocket. An adjacent hydrophobic helical element packs against the acyl chains and inserts robustly into PI(4)P-containing monolayers. The structural, biochemical, and biophysical data reported here support a detailed structural mechanism for PI(4)P-dependent membrane targeting by DrrA.

PubMed: 24530282
DOI: 10.1016/j.str.2013.12.018

実験手法

X-RAY DIFFRACTION (1.83 Å)