title: Nuclear import mechanism of the EJC component Mago-Y14 revealed by structural studies of importin 13.
abstract: Mago and Y14 are core components of the exon junction complex (EJC), an assembly central to nonsense-mediated mRNA decay in humans and mRNA localization in flies. The Mago-Y14 heterodimer shuttles between the nucleus, where it is loaded onto specific mRNAs, and the cytoplasm, where it functions in translational regulation. The heterodimer is imported back into the nucleus by Importin 13 (Imp13), a member of the karyopherin-beta family of transport factors. We have elucidated the structural basis of the Mago-Y14 nuclear import cycle. The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface. The 2.8 A structure of human Imp13 bound to RanGTP reveals how Mago-Y14 is released in the nucleus by a steric hindrance mechanism. Comparison of the two structures suggests how this unusual karyopherin might function in bidirectional nucleocytoplasmic transport.
authors.affiliation: Max-Planck-Institute of Biochemistry, Department of Structural Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bono
authors.forename: Atlanta G
authors.initials: AG
authors.lastname: Cook
authors.forename: Marlene
authors.initials: M
authors.lastname: Grünwald
authors.forename: Judith
authors.initials: J
authors.lastname: Ebert
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D028884:Karyopherins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D028884:Karyopherins; C107372:Mago protein, Drosophila; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C540911:cdm protein, Drosophila; C440016:tsu protein, Drosophila; D020931:ran GTP-Binding Protein