The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor

Science. 2003 Nov 28;302(5650):1571-5. doi: 10.1126/science.1088372.


The sterol regulatory element-binding protein 2 (SREBP-2), a nuclear transcription factor that is essential for cholesterol metabolism, enters the nucleus through a direct interaction of its helix-loop-helix leucine zipper domain with importin-beta. We show the crystal structure of importin-beta complexed with the active form of SREBP-2. Importin-beta uses characteristic long helices like a pair of chopsticks to interact with an SREBP-2 dimer. Importin-beta changes its conformation to reveal a pseudo-twofold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. Importin-beta may use a similar strategy to recognize other dimeric cargoes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Nucleus / metabolism
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Helix-Loop-Helix Motifs
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Localization Signals
  • Nuclear Pore / metabolism
  • Protein Binding
  • Protein Conformation*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*
  • beta Karyopherins / chemistry*
  • beta Karyopherins / metabolism*
  • ran GTP-Binding Protein / metabolism


  • DNA-Binding Proteins
  • Nuclear Localization Signals
  • SREBF2 protein, human
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors
  • beta Karyopherins
  • ran GTP-Binding Protein