Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking.
We describe the crystal structure of a complex between importin-beta residues 1-442 (Ib442) and five FxFG nucleoporin repeats from Nsp1p. Nucleoporin FxFG cores bind on the convex face of Ib442 to a primary site between the A helices of HEAT repeats 5 and 6, and to a secondary site between HEAT repeats 6 and 7. Mutations at importin-beta Ile178 in the primary FxFG binding site reduce both binding and nuclear protein import, providing direct evidence for the functional significance of the importin-beta-FxFG interaction. The FxFG binding sites on importin-beta do not overlap with the RanGTP binding site. Instead, RanGTP may release importin-beta from FxFG nucleoporins by generating a conformational change that alters the structure of the FxFG binding site.
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
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Bayliss
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Littlewood
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Stewart
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002135:Calcium-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D020080:Tandem Repeat Sequences; D020931:ran GTP-Binding Protein / Q000378:metabolism
D002135:Calcium-Binding Proteins; D005656:Fungal Proteins; D028884:Karyopherins; C062748:NSP1 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D020931:ran GTP-Binding Protein