Disease relevance of NTF2

• The mutant NTF2 cDNAs were expressed in Escherichia coli [1].

High impact information on NTF2

• Role of the nuclear transport factor p10 in nuclear import [2].
• Engineered mutants at the interaction interface reduce the binding of NTF2 to nuclear pores and cause reduced growth rates and Ran mislocalization when substituted for the wild-type protein in yeast [3].
• The two identical FxFG binding sites on the dimeric molecule are formed by residues from each chain of NTF2 [3].
• Our data suggest that NTF2 acts at a relatively late stage of nuclear protein import, subsequent to the initial docking of nuclear import ligand at the nuclear envelope [4].
• We obtained a cDNA encoding NTF2 and showed that the recombinant protein restores transport activity to p62-pretreated cytosol [4].

Biological context of NTF2

• Overexpression of NTF2 can suppress the temperature sensitive phenotype of gsp1-1 and gsp1-2 and partially rescue nuclear transport defects [5].
• In the present study we have used molecular genetic approaches to study the Saccharomyces cerevisiae homologue of NTF2 [6].
• Mog1p and NTF2 compete for binding to RanGDP indicating that their binding sites on RanGDP are sufficiently close to prevent both proteins binding simultaneously [7].
• Here we present the first evidence that demonstrates an essential in vivo role for the NTF2 gene product in nuclear transport [8].
• The interaction between Ran and NTF2 is required for cell cycle progression [9].

Anatomical context of NTF2

• Previous biochemical studies have shown that NTF2 binds directly to the GDP-bound form of Ran/TC4 and to proteins of the nuclear pore complex that contain phenylalanine-glycine repeats [6].

Associations of NTF2 with chemical compounds

• Proteins that regulate the GTPase cycle and subcellular distribution of Ran include the cytoplasmic GTPase-activating protein (RanGAP) and its co-factors (RanBP1, RanBP2), the nuclear guanine nucleotide exchange factor (RanGEF), and the Ran import receptor (NTF2) [10].
• Comparison of the sequences of the xFxFG repeat regions of p62 and Nsplp indicated that NTF2 was probably interacting with the phenylalanine-containing core of these repeats and not the intervening hydrophilic linkers [11].

Physical interactions of NTF2

• Thus, Mog1p, which was localized in the nucleus, is a Gsp1p-binding protein involved in nuclear-protein import and that functionally interacts with Ntf2p [12].

Other interactions of NTF2

• Both biochemical and genetic experiments indicate a decreased interaction between Ntf2p, a factor which is required for protein import, and the mutant GSP1 gene products [5].
• In this study, we report the x-ray crystal structure of the Bre5 NTF2-like domain and show that it forms a homodimeric structure that is similar to other NTF2-like domains, except for the presence of an intermolecular disulfide bond in the crystals [13].
• Based on these data, we obtained crystals of complexes between yeast NTF2 and a construct containing five FxFG nucleoporin repeats from the yeast nucleoporin Nsp1p and between a construct containing residues 1-442 of human importin-beta and the same nucleoporin construct [14].

Analytical, diagnostic and therapeutic context of NTF2

• We employed a native gel electrophoresis method to assess the interaction of nucleoporin constructs that contain FxFG sequence repeats with NTF2 and truncation mutants of importin-beta to determine suitable fragments for crystallization [14].

References