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.
MeSH terms
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Bacterial Proteins / chemistry*
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Bacterial Proteins / metabolism*
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Binding Sites
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Crystallography, X-Ray
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Guanine Nucleotide Exchange Factors / chemistry*
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Guanine Nucleotide Exchange Factors / metabolism*
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Humans
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Legionella pneumophila / chemistry
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Legionella pneumophila / metabolism
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Legionella pneumophila / pathogenicity*
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Models, Molecular
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Molecular Sequence Data
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Phagocytosis / physiology
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Phosphatidylinositol Phosphates / chemistry*
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Phosphatidylinositol Phosphates / metabolism*
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Protein Binding
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Protein Conformation
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Protein Interaction Domains and Motifs
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rab1 GTP-Binding Proteins / metabolism
Substances
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Bacterial Proteins
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Guanine Nucleotide Exchange Factors
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Phosphatidylinositol Phosphates
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SidM protein, Legionella pneumophila
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phosphatidylinositol 4-phosphate
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rab1 GTP-Binding Proteins