title: The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore.
abstract: Nuclear export of mRNA in eukaryotic cells is mediated by soluble transport factors and components of the nuclear pore complex (NPC). The cytoplasmically oriented nuclear pore protein Nup159 plays a critical role in mRNA export through its conserved N-terminal domain (NTD). Here, we report the crystal structure of the Nup159 NTD, refined to 2.5 A. The structure reveals an unusually asymmetric seven-bladed beta-propeller that is structurally conserved throughout eukarya. Using structure-based conservation analysis, we have targeted specific surface residues for mutagenesis. Residue substitutions in a conserved loop of the NTD abolish in vitro binding to Dbp5, a DEAD box helicase required for mRNA export. In vivo, these mutations cause Dbp5 mislocalization and block mRNA export. These findings suggest that the Nup159 NTD functions in mRNA export as a binding platform, tethering shuttling Dbp5 molecules at the nuclear periphery and locally concentrating this mRNA remodeling factor at the cytoplasmic face of the NPC.
authors.affiliation: Division of Cell and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Weirich
authors.forename: Jan P
authors.initials: JP
authors.lastname: Erzberger
authors.forename: James M
authors.initials: JM
authors.lastname: Berger
authors.forename: Karsten
authors.initials: K
authors.lastname: Weis
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D017403:In Situ Hybridization; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: C093510:NUP159 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C492382:DBP5 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases