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Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin α

Nature Structural Biology volume 6, pages 388–397 (1999)Cite this article

Abstract

Importin α is the nuclear import receptor that recognizes classical monopartite and bipartite nuclear localization signals (NLSs). The structure of mouse importin α has been determined at 2.5 Å resolution. The structure shows a large C-terminal domain containing armadillo repeats, and a less structured N-terminal importin β-binding domain containing an internal NLS bound to the NLS-binding site. The structure explains the regulatory switch between the cytoplasmic, high-affinity form, and the nuclear, low-affinity form for NLS binding of the nuclear import receptor predicted by the current models of nuclear import. Importin β conceivably converts the low- to high-affinity form by binding to a site overlapping the autoinhibitory sequence. The structure also has implications for understanding NLS recognition, and the structures of armadillo and HEAT repeats.

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Figure 1: Structure of mouse importin α.
Figure 2: Comparison of mouse and yeast importin α.
Figure 3: Mechanism of autoinhibition.
Figure 4: Mechanism of autoinhibition.
Figure 5: Schematic diagram illustrating the proposed NLS-dependent import pathway.
Figure 6: NLS-binding determinants.
Figure 7: Armadillo and HEAT repeats.

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Acknowledgements

I thank T. Teh, T. Tiganis, M. Lam, B. Kemp, J. Horne and T. Gleichmann for help and discussions, and J. Kuriyan and coworkers for making the coordinates of yeast Kapα50 available on their web site before the release by the Protein Data Bank. I apologize to those whose original publications could not be cited because of space limitations. This work was supported by the Wellcome Trust and the National Health and Medical Research Council; B.K. is a Wellcome Senior Research Fellow in Medical Science in Australia.

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  1. Structural Biology Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, 41 Victoria Parade, Victoria, 3065, Australia

    Bostjan Kobe

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Kobe, B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin α. Nat Struct Mol Biol 6, 388–397 (1999). https://doi.org/10.1038/7625

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