title: High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA.
abstract: The DrrA protein of Legionella pneumophila is involved in mistargeting of endoplasmic reticulum-derived vesicles to Legionella-containing vacuoles through recruitment of the small GTPase Rab1. To this effect, DrrA binds specifically to phosphatidylinositol 4-phosphate (PtdIns(4)P) lipids on the cytosolic surface of the phagosomal membrane shortly after infection. In this study, we present the atomic structure of the PtdIns(4)P-binding domain of a protein (DrrA) from a human pathogen. A detailed kinetic investigation of its interaction with PtdIns(4)P reveals that DrrA binds to this phospholipid with, as yet unprecedented, high affinity, suggesting that DrrA can sense a very low abundance of the lipid.
authors.affiliation: Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, North Rhine-Westphalia, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoebel
authors.forename: Wulf
authors.initials: W
authors.lastname: Blankenfeldt
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Aymelt
authors.initials: A
authors.lastname: Itzen
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D016952:Legionella pneumophila / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; C539733:SidM protein, Legionella pneumophila; C037178:phosphatidylinositol 4-phosphate; D020761:rab1 GTP-Binding Proteins