Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.
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.
Misra
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Laboratory of Molecular Biology, National Institute of Digestive, Diabetes, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA.
Hurley
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D018129:Phosphatidylinositol Phosphates; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C119627:VPS27 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C055525:phosphatidylinositol 3-phosphate