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Cell biology

Snail mail to the nucleus

Nature volume 399, pages 208–210 (1999)Cite this article

All members of the importin-β family interact with the GTP-bound form of a small GTPase called Ran. When Ran⃛GTP binds to importins, it causes release of the cargo (Fig. 1a); in contrast, exportins bind to their cargo only in the presence of Ran·GTP ( Fig. 1b). The direction of transport depends on the concentration of Ran·GTP, which needs to be high in the nucleus and low in the cytoplasm1. But how does binding of Ran·GTP affect the conformations of the receptors — and, so, their ability to interact with cargo? The two new receptor structures2,3, one with bound cargo and the other with Ran·GTP, provide the first insights into this conformational switch.

The two receptors consist of protein motifs called HEAT repeats7 (Fig. 2), arranged in right-handed superhelical structures. The basic HEAT repeat consists of a hairpin made up of two α-helices2,8 (called the A and B helices) separated by a sharp turn. A linker region connects each hairpin to the next. The A helices form the convex outer surface of the proteins, whereas the concave, inner surface of each protein is lined by B helices. This inner surface interacts directly with Ran·GTP and the IBB domain. In Kap β2, almost all of the linkers contain a third α-helix3, but there are few linker helices in importin β2. In both receptors, one of the sharp turns is extended into a long, acidic loop, which is probably critical for Ran·GTP-mediated cargo release2,3.

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Figure 1: Nuclear import and export cycles.
Figure 2: Comparison of importin β and transportin/Karyopherin β2 (Kap β2).

References

  1. Mattaj, I. W. & Englmeier, L. Annu. Rev. Biochem. 67, 265–306 (1998).

    Google Scholar 

  2. Cingolani, G., Petosa, C., Weis, K. & Müller, C. W. Nature 399, 221–229 ( 1999).

    Article  ADS  CAS  Google Scholar 

  3. Chook, Y. M. & Blobel, G. Nature 399, 230–237 (1999).

    Article  ADS  CAS  Google Scholar 

  4. Görlich, D., Henklein, P., Laskey, R. A. & Hartmann, E. EMBO J. 15, 1810–1817 ( 1996).

    Google Scholar 

  5. Weis, K., Ryder, U. & Lamond, A. I. EMBO J. 15, 1818– 1825 (1996).

    Google Scholar 

  6. Pollard, V. W. et al. Cell 86, 985–994 (1996).

    Google Scholar 

  7. Andrade, M. A. & Bork, P. Nature Genet. 11, 115–116 (1995).

    Google Scholar 

  8. Groves, M. R., Hanlon, N., Turowski, P., Hemmings, B. A. & Bradford, D. Cell 96, 99– 110 (1999).

    Google Scholar 

  9. Vetter, I. R., Nowak, C., Nishimoto, T., Kühlmann, J. & Wittinghoferr, A. Nature 398, 39– 46 (1999).

    Article  ADS  CAS  Google Scholar 

  10. Scheffzek, K., Klebe, C., Fritz-Wolf, K., Kabsch, W. & Wittinghoferr, A. Nature 374, 378–381 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Fridell, R. A. et al. J. Cell Sci. 110, 1325– 1331 (1997).

    Google Scholar 

  12. Moroianu, J., Hijikata, M., Blobel, G. & Radu, A. Proc. Natl Acad. Sci. USA 92, 6532–6536 ( 1995).

    Google Scholar 

  13. Moroianu, J., Blobel, G. & Radu, A. Proc. Natl Acad. Sci. USA 93, 6572 –6576 (1996).

    Google Scholar 

Download references

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Authors and Affiliations

  1. the European Molecular Biology Laboratory, Meyerhofstrae 1, Heidelberg, 69117, Germany

    Iain W. Mattaj & Elena Conti

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  1. Iain W. Mattaj
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  2. Elena Conti
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Mattaj, I., Conti, E. Snail mail to the nucleus. Nature 399, 208–210 (1999). https://doi.org/10.1038/20322

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