title: Structure of a Ca2+-myristoyl switch protein that controls activation of a phosphatidylinositol 4-kinase in fission yeast.
abstract: Neuronal calcium sensor (NCS) proteins transduce Ca2+ signals and are highly conserved from yeast to humans. We determined NMR structures of the NCS-1 homolog from fission yeast (Ncs1), which activates a phosphatidylinositol 4-kinase. Ncs1 contains an α-NH2-linked myristoyl group on a long N-terminal arm and four EF-hand motifs, three of which bind Ca2+, assembled into a compact structure. In Ca2+-free Ncs1, the N-terminal arm positions the fatty acyl chain inside a cavity near the C terminus. The C14 end of the myristate is surrounded by residues in the protein core, whereas its amide-linked (C1) end is flanked by residues at the protein surface. In Ca2+-bound Ncs1, the myristoyl group is extruded (Ca2+-myristoyl switch), exposing a prominent patch of hydrophobic residues that specifically contact phosphatidylinositol 4-kinase. The location of the buried myristate and structure of Ca2+-free Ncs1 are quite different from those in other NCS proteins. Thus, a unique remodeling of each NCS protein by its myristoyl group, and Ca2+-dependent unmasking of different residues, may explain how each family member recognizes distinct target proteins.
authors.affiliation: Department of Chemistry, University of California, Davis, California 95616, USA.
authors.forename: Sunghyuk
authors.initials: S
authors.lastname: Lim
authors.forename: Thomas
authors.initials: T
authors.lastname: Strahl
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.forename: James B
authors.initials: JB
authors.lastname: Ames
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D005656:Fungal Proteins; D051580:Neuronal Calcium-Sensor Proteins; D019814:Myristic Acid; D019870:1-Phosphatidylinositol 4-Kinase; D002118:Calcium