The Structure of Importin-ß Bound to SREBP-2: Nuclear Import of a Transcription Factor

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-β. We show the crystal structure of importin-β complexed with the active form of SREBP-2. Importin-β uses characteristic long helices like a pair of chopsticks to interact with an SREBP-2 dimer. Importin-β changes its conformation to reveal a pseudo-twofold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. Importin-β may use a similar strategy to recognize other dimeric cargoes.