The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding

Atlanta Cook, Elena Fernandez, Doris Lindner, Judith Ebert, Gabriel Schlenstedt, Elena Conti

Research output: Contribution to journalArticlepeer-review

Abstract

Cse1 mediates nuclear export of importin alpha, the nuclear localization signal (NLS) import adaptor. We report the 3.1 A resolution structure of cargo-free Cse1, representing this HEAT repeat protein in its cytosolic state. Cse1 is compact, consisting of N- and C-terminal arches that interact to form a ring. Comparison with the structure of cargo-bound Cse1 shows a major conformational change leading to opening of the structure upon cargo binding. The largest structural changes occur within a hinge region centered at HEAT repeat 8. This repeat contains a conserved insertion that connects the RanGTP and importin alpha contact sites and that is essential for binding. In the cargo-free state, the RanGTP binding sites are occluded and the importin alpha sites are distorted. Mutations that destabilize the N- to C-terminal interaction uncouple importin alpha and Ran binding, suggesting that the closed conformation prevents association with importin alpha.
Original languageEnglish
Pages (from-to)355-67
Number of pages13
JournalMolecular Cell
Volume18
Issue number3
DOIs
Publication statusPublished - 2005

Keywords

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins
  • Sequence Alignment
  • alpha Karyopherins
  • ran GTP-Binding Protein

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