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Science 28 November 2003:
Vol. 302. no. 5650, pp. 1571 - 1575
DOI: 10.1126/science.1088372
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Reports

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

Soo Jae Lee,1,2 Toshihiro Sekimoto,2 Eiki Yamashita,1 Emi Nagoshi,2 Atsushi Nakagawa,1 Naoko Imamoto,2 Masato Yoshimura,1 Hiroaki Sakai,1 Khoon Tee Chong,1 Tomitake Tsukihara,1* Yoshihiro Yoneda2*

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

1 Institute for Protein Research, Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 2-2, Suita, Osaka 565–0871, Japan.
2 Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 2-2, Suita, Osaka 565–0871, Japan.

* To whom correspondence should be addressed. E-mail: tsuki{at}protein.osaka-u.ac.jp (T.T.); yyoneda{at}anat3.med.osaka-u.ac.jp (Y.Y.)

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