4MXP

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

Summary for 4MXP

• Entry DOI: 10.2210/pdb4mxp/pdb
• Descriptor: 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)
• Functional Keywords: protein-lipid complex, guanine nucleotide exchange factor, rab1 binding, pi(4)p-binding protein
• Biological source: Legionella pneumophila subsp. pneumophila
• Cellular location: Secreted: Q5ZSQ3
• Total number of polymer chains: 1
• Total formula weight: 37691.56

Authors

Del Campo, C.M.,Mishra, A.K.,Wang, Y.H.,Roy, C.R.,Janmey, P.A.,Lambright, D.G. (deposition date: 2013-09-26, release date: 2014-03-19, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.83 Å)