title: Crystal structure of the N-terminal domain of Nup358/RanBP2.
abstract: Key steps in mRNA export are the nuclear assembly of messenger ribonucleoprotein particles (mRNPs), the translocation of mRNPs through the nuclear pore complex (NPC), and the mRNP remodeling events at the cytoplasmic side of the NPC. Nup358/RanBP2 is a constituent of the cytoplasmic filaments of the NPC specific to higher eukaryotes and provides a multitude of binding sites for the nucleocytoplasmic transport machinery. Here, we present the crystal structure of the Nup358 N-terminal domain (NTD) at 0.95Å resolution. The structure reveals an α-helical domain that harbors three central tetratricopeptide repeats (TPRs), flanked on each side by an additional solvating amphipathic α helix. Overall, the NTD adopts an unusual extended conformation that lacks the characteristic peptide-binding groove observed in canonical TPR domains. Strikingly, the vast majority of the NTD surface exhibits an evolutionarily conserved, positive electrostatic potential, and we demonstrate that the NTD possesses the capability to bind single-stranded RNA in solution. Together, these data suggest that the NTD contributes to mRNP remodeling events at the cytoplasmic face of the NPC.
authors.affiliation: Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Kassube
authors.forename: Tobias
authors.initials: T
authors.lastname: Stuwe
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lin
authors.forename: C Danielle
authors.initials: CD
authors.lastname: Antonuk
authors.forename: Johanna
authors.initials: J
authors.lastname: Napetschnig
authors.forename: Günter
authors.initials: G
authors.lastname: Blobel
authors.forename: André
authors.initials: A
authors.lastname: Hoelz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2; D012313:RNA