The N-terminal domain of Nup159 forms a β-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore

Christine S. Weirich, Jan P. Erzberger, James M. Berger, Karsten Weis

Research output: Contribution to journalArticle

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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 Å. The structure reveals an unusually asymmetric seven-bladed β-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.

Original languageEnglish (US)
Pages (from-to)749-760
Number of pages12
JournalMolecular Cell
Volume16
Issue number5
DOIs
StatePublished - Dec 3 2004

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Nuclear Pore
Messenger RNA
Porins
Cell Nucleus Active Transport
Eukaryotic Cells
Nuclear Proteins
Eukaryota
Mutagenesis
Mutation

ASJC Scopus subject areas

  • Molecular Biology

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The N-terminal domain of Nup159 forms a β-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. / Weirich, Christine S.; Erzberger, Jan P.; Berger, James M.; Weis, Karsten.

In: Molecular Cell, Vol. 16, No. 5, 03.12.2004, p. 749-760.

Research output: Contribution to journalArticle

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