Abstract
Phosphatidylinositol 3-phosphate regulates membrane trafficking and signaling pathways by interacting with the FYVE domains of target proteins. The 1.15 A structure of the Vps27p FYVE domain reveals two antiparallel beta sheets and an alpha helix stabilized by two Zn2+-binding clusters. The core secondary structures are similar to a rabphilin-3A Zn2+-binding domain and to the C1 and LIM domains. Phosphatidylinositol 3-phosphate binds to a pocket formed by the (R/K)(R/K)HHCR motif. A lattice contact shows how anionic ligands can interact with the phosphatidylinositol 3-phosphate-binding site. The tip of the FYVE domain has basic and hydrophobic surfaces positioned so that nonspecific interactions with the phospholipid bilayer can abet specific binding to phosphatidylinositol 3-phosphate.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Cell Membrane / metabolism
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Crystallography, X-Ray
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Endosomal Sorting Complexes Required for Transport
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Fungal Proteins / chemistry*
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Fungal Proteins / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Phosphatidylinositol Phosphates / chemistry
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Phosphatidylinositol Phosphates / metabolism*
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Vesicular Transport Proteins*
Substances
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Carrier Proteins
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Endosomal Sorting Complexes Required for Transport
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Fungal Proteins
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Phosphatidylinositol Phosphates
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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VPS27 protein, S cerevisiae
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Vesicular Transport Proteins
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phosphatidylinositol 3-phosphate