title: The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor.
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.
authors.affiliation: Institute for Protein Research, Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: Soo Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamashita
authors.forename: Emi
authors.initials: E
authors.lastname: Nagoshi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Khoon Tee
authors.initials: KT
authors.lastname: Chong
authors.forename: Tomitake
authors.initials: T
authors.lastname: Tsukihara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019281:Dimerization; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D022022:Nuclear Pore / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; C497390:SREBF2 protein, human; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein