The structure of importin-beta 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-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.
Lee
Soo Jae
SJ
Institute for Protein Research, Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
Sekimoto
Toshihiro
T
Yamashita
Eiki
E
Nagoshi
Emi
E
Nakagawa
Atsushi
A
Imamoto
Naoko
N
Yoshimura
Masato
M
Sakai
Hiroaki
H
Chong
Khoon Tee
KT
Tsukihara
Tomitake
T
Yoneda
Yoshihiro
Y
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
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