Structural basis for nuclear import complex dissociation by RanGTP

Nature. 2005 Jun 2;435(7042):693-6. doi: 10.1038/nature03578. Epub 2005 May 1.


Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Allosteric Regulation
  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism*
  • Mutation / genetics
  • Protein Conformation
  • Saccharomyces cerevisiae
  • Structure-Activity Relationship
  • beta Karyopherins / chemistry*
  • beta Karyopherins / metabolism*
  • ran GTP-Binding Protein / chemistry*
  • ran GTP-Binding Protein / genetics
  • ran GTP-Binding Protein / metabolism*


  • Multiprotein Complexes
  • beta Karyopherins
  • ran GTP-Binding Protein

Associated data

  • PDB/2BKU