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

Lee, Soo Jae; Sekimoto, Toshihiro; Yamashita, Eiki; Nagoshi, Emi; Nakagawa, Atsushi; Imamoto, Naoko; Yoshimura, Masato; Sakai, Hiroaki et al. · Science · 2003

basic_science · Level V

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Abstract

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.

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