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| Subject Categories: Membranes & Transport | Structural Biology |
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| The EMBO Journal
(2005) 24, 3681–3689, doi:10.1038/sj.emboj.7600843 Published online 13 October 2005 |
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| Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling |
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| Yoshiyuki Matsuura1, 2 and Murray Stewart1 |
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1 MRC Laboratory of Molecular Biology, Cambridge, UK 2 Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan To whom correspondence should be addressed Murray Stewart, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402463; Fax: +44 1223 213556; E-mail: ms@mrc-lmb.cam.ac.uk Received 1 June 2005; Accepted 20 September 2005; Published online 13 October 2005. |
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| Abstract |
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Nuclear import of proteins containing classical nuclear localization signals (NLS) is mediated by the importin- : complex that binds cargo in the cytoplasm and facilitates its passage through nuclear pores, after which nuclear RanGTP dissociates the import complex and the importins are recycled. In vertebrates, import is stimulated by nucleoporin Nup50, which has been proposed to accompany the import complex through nuclear pores. However, we show here that the Nup50 N-terminal domain actively displaces NLSs from importin-, which would be more consistent with Nup50 functioning to coordinate import complex disassembly and importin recycling. The crystal structure of the importin-:Nup50 complex shows that Nup50 binds at two sites on importin-. One site overlaps the secondary NLS-binding site, whereas the second extends along the importin- C-terminus. Mutagenesis indicates that interaction at both sites is required for Nup50 to displace NLSs. The Cse1p:Kap60p:RanGTP complex structure suggests how Nup50 is then displaced on formation of the importin- export complex. These results provide a rationale for understanding the series of interactions that orchestrate the terminal steps of nuclear protein import. |
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| Keywords: importin, NLS, nuclear pore, Nup50, Nup2p |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Structural & Molecular Biology News and Views (01 Jun 2006) Switching affinities in nuclear trafficking Nature Structural Biology News and Views (01 Apr 1999) RESEARCHStructural basis for Nup2p function in cargo release and karyopherin recycling in nuclear import The EMBO Journal Article (15 Oct 2003) Structural basis for Nup2p function in cargo release and karyopherin recycling in nuclear import The EMBO Journal Article (15 Oct 2003) |
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