2c1m: Difference between revisions

Revision as of 17:43, 21 February 2008

NUP50:IMPORTIN-ALPHA COMPLEX

OverviewOverview

Nuclear import of proteins containing classical nuclear localization signals (NLS) is mediated by the importin-alpha:beta 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-alpha, which would be more consistent with Nup50 functioning to coordinate import complex disassembly and importin recycling. The crystal structure of the importin-alpha:Nup50 complex shows that Nup50 binds at two sites on importin-alpha. One site overlaps the secondary NLS-binding site, whereas the second extends along the importin-alpha 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-alpha export complex. These results provide a rationale for understanding the series of interactions that orchestrate the terminal steps of nuclear protein import.

About this StructureAbout this Structure

2C1M is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling., Matsuura Y, Stewart M, EMBO J. 2005 Nov 2;24(21):3681-9. Epub 2005 Oct 13. PMID:16222336

Page seeded by OCA on Thu Feb 21 16:43:53 2008

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OCA

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-[[Image:2c1m.gif|left|200px]]<br /><applet load="2c1m" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="2c1m, resolution 2.20&Aring;" />
 '''NUP50:IMPORTIN-ALPHA COMPLEX'''<br />
 ==Overview==
-Nuclear import of proteins containing classical nuclear localization, signals (NLS) is mediated by the importin-alpha:beta 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-alpha, which would be more, consistent with Nup50 functioning to coordinate import complex disassembly, and importin recycling. The crystal structure of the importin-alpha:Nup50, complex shows that Nup50 binds at two sites on importin-alpha. One site, overlaps the secondary NLS-binding site, whereas the second extends along, the importin-alpha 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-alpha export complex. These results provide a rationale for, understanding the series of interactions that orchestrate the terminal, steps of nuclear protein import.
+Nuclear import of proteins containing classical nuclear localization signals (NLS) is mediated by the importin-alpha:beta 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-alpha, which would be more consistent with Nup50 functioning to coordinate import complex disassembly and importin recycling. The crystal structure of the importin-alpha:Nup50 complex shows that Nup50 binds at two sites on importin-alpha. One site overlaps the secondary NLS-binding site, whereas the second extends along the importin-alpha 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-alpha export complex. These results provide a rationale for understanding the series of interactions that orchestrate the terminal steps of nuclear protein import.
 ==About this Structure==
-C1M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C1M OCA].
+C1M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C1M OCA].
 ==Reference==
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 [[Category: protein transport]]
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