Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking

Cell. 2000 Jul 7;102(1):99-108. doi: 10.1016/s0092-8674(00)00014-3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Transport
  • Calcium-Binding Proteins*
  • Cell Nucleus / metabolism
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Karyopherins
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Tandem Repeat Sequences*
  • ran GTP-Binding Protein / metabolism

Substances

  • Calcium-Binding Proteins
  • Fungal Proteins
  • Karyopherins
  • NSP1 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • ran GTP-Binding Protein

Associated data

  • PDB/1F59