The structure of importin-β bound to SREBP-2:: Nuclear import of a transcription factor

被引:181
作者
Lee, SJ
Sekimoto, T
Yamashita, E
Nagoshi, E
Nakagawa, A
Imamoto, N
Yoshimura, M
Sakai, H
Chong, KT
Tsukihara, T
Yoneda, Y
机构
[1] Osaka Univ, Grad Sch Frontier Biosci, Dept Frontier Biosci, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan
关键词
D O I
10.1126/science.1088372
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1571 / 1575
页数:5
相关论文
共 34 条
  • [1] [Anonymous], METHOD ENZYMOL
  • [2] Structural basis for the interaction between FxFG nucleoporin repeats and importin-β in nuclear trafficking
    Bayliss, R
    Littlewood, T
    Stewart, M
    [J]. CELL, 2000, 102 (01) : 99 - 108
  • [3] The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor
    Brown, MS
    Goldstein, JL
    [J]. CELL, 1997, 89 (03) : 331 - 340
  • [4] Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery
    Chan, CK
    Hubner, S
    Hu, W
    Jans, DA
    [J]. GENE THERAPY, 1998, 5 (09) : 1204 - 1212
  • [5] Molecular basis for the recognition of a nonclassical nuclear localization signal by importin β
    Cingolani, G
    Bednenko, J
    Gillespie, MT
    Gerace, L
    [J]. MOLECULAR CELL, 2002, 10 (06) : 1345 - 1353
  • [6] Structure of importin-β bound to tbe IBB domain of importin-α
    Cingolani, G
    Petosa, C
    Weis, K
    Müller, CW
    [J]. NATURE, 1999, 399 (6733) : 221 - 229
  • [7] Nucleocytoplasmic transport of macromolecules
    Corbett, AH
    Silver, PA
    [J]. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 1997, 61 (02) : 193 - +
  • [8] Cowtan K., 1994, JOINT CCP4 ESF EACBM, V31, P34
  • [9] IDENTIFICATION OF THE HUMAN C-MYC PROTEIN NUCLEAR TRANSLOCATION SIGNAL
    DANG, CV
    LEE, WMF
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (10) : 4048 - 4054
  • [10] RECOGNITION BY MAX OF ITS COGNATE DNA THROUGH A DIMERIC B/HLH/Z DOMAIN
    FERREDAMARE, AR
    PRENDERGAST, GC
    ZIFF, EB
    BURLEY, SK
    [J]. NATURE, 1993, 363 (6424) : 38 - 45