Structural basis for the assembly of a nuclear export complex
- PMID: 15602554
- DOI: 10.1038/nature03144
Structural basis for the assembly of a nuclear export complex
Abstract
The nuclear import and export of macromolecular cargoes through nuclear pore complexes is mediated primarily by carriers such as importin-beta. Importins carry cargoes into the nucleus, whereas exportins carry cargoes to the cytoplasm. Transport is orchestrated by nuclear RanGTP, which dissociates cargoes from importins, but conversely is required for cargo binding to exportins. Here we present the 2.0 A crystal structure of the nuclear export complex formed by exportin Cse1p complexed with its cargo (Kap60p) and RanGTP, thereby providing a structural framework for understanding nuclear protein export and the different functions of RanGTP in export and import. In the complex, Cse1p coils around both RanGTP and Kap60p, stabilizing the RanGTP-state and clamping the Kap60p importin-beta-binding domain, ensuring that only cargo-free Kap60p is exported. Mutagenesis indicated that conformational changes in exportins couple cargo binding to high affinity for RanGTP, generating a spring-loaded molecule to facilitate disassembly of the export complex following GTP hydrolysis in the cytoplasm.
Comment in
-
Cell biology: popping out of the nucleus.Nature. 2004 Dec 16;432(7019):815-6. doi: 10.1038/432815a. Nature. 2004. PMID: 15602540 No abstract available.
Similar articles
-
Structural basis for nuclear import complex dissociation by RanGTP.Nature. 2005 Jun 2;435(7042):693-6. doi: 10.1038/nature03578. Epub 2005 May 1. Nature. 2005. PMID: 15864302
-
The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding.Mol Cell. 2005 Apr 29;18(3):355-67. doi: 10.1016/j.molcel.2005.03.021. Mol Cell. 2005. PMID: 15866177
-
Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP.Science. 2009 May 22;324(5930):1087-91. doi: 10.1126/science.1173388. Epub 2009 Apr 23. Science. 2009. PMID: 19389996
-
Structural biology of nucleocytoplasmic transport.Annu Rev Biochem. 2007;76:647-71. doi: 10.1146/annurev.biochem.76.052705.161529. Annu Rev Biochem. 2007. PMID: 17506639 Review.
-
Mechanistic Insights from Structural Analyses of Ran-GTPase-Driven Nuclear Export of Proteins and RNAs.J Mol Biol. 2016 May 22;428(10 Pt A):2025-39. doi: 10.1016/j.jmb.2015.09.025. Epub 2015 Oct 28. J Mol Biol. 2016. PMID: 26519791 Review.
Cited by
-
Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors.PLoS One. 2009 Dec 24;4(12):e8420. doi: 10.1371/journal.pone.0008420. PLoS One. 2009. PMID: 20041180 Free PMC article.
-
Deciphering the Structure and Function of Nuclear Pores Using Single-Molecule Fluorescence Approaches.J Mol Biol. 2016 May 22;428(10 Pt A):2091-119. doi: 10.1016/j.jmb.2016.02.023. Epub 2016 Mar 2. J Mol Biol. 2016. PMID: 26944195 Free PMC article. Review.
-
Structures of the pleckstrin homology domain of Saccharomyces cerevisiae Avo1 and its human orthologue Sin1, an essential subunit of TOR complex 2.Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):386-92. doi: 10.1107/S1744309112007178. Epub 2012 Mar 27. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012. PMID: 22505404 Free PMC article.
-
A protein interaction network for Ecm29 links the 26 S proteasome to molecular motors and endosomal components.J Biol Chem. 2010 Oct 8;285(41):31616-33. doi: 10.1074/jbc.M110.154120. Epub 2010 Aug 3. J Biol Chem. 2010. PMID: 20682791 Free PMC article.
-
Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling.EMBO J. 2005 Nov 2;24(21):3681-9. doi: 10.1038/sj.emboj.7600843. Epub 2005 Oct 13. EMBO J. 2005. PMID: 16222336 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
