Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Biological Transport
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Calcium-Binding Proteins*
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Cell Nucleus / metabolism
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Crystallography, X-Ray
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Fungal Proteins / chemistry
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Fungal Proteins / metabolism*
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HeLa Cells
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Humans
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Karyopherins
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis
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Nuclear Pore Complex Proteins
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Protein Structure, Secondary
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
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Tandem Repeat Sequences*
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ran GTP-Binding Protein / metabolism
Substances
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Calcium-Binding Proteins
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Fungal Proteins
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Karyopherins
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NSP1 protein, S cerevisiae
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Nuclear Pore Complex Proteins
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Nuclear Proteins
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Saccharomyces cerevisiae Proteins
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ran GTP-Binding Protein