Document Detail


Structural basis for the assembly of a nuclear export complex.
MedLine Citation:
PMID:  15602554     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yoshiyuki Matsuura; Murray Stewart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  432     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-16     Completed Date:  2005-01-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  872-7     Citation Subset:  IM    
Affiliation:
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Data Bank Information
Bank Name/Acc. No.:
PDB/1WA5;  RLWA5SF
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Binding Sites
Crystallography, X-Ray
Guanosine Triphosphate / metabolism
Models, Molecular
Multiprotein Complexes
Nuclear Pore / chemistry*,  metabolism*
Nuclear Pore Complex Proteins / chemistry*,  metabolism*
Nuclear Proteins / chemistry,  metabolism
Nucleocytoplasmic Transport Proteins
Protein Binding
Protein Conformation
Protein Transport
Saccharomyces cerevisiae / cytology,  metabolism
Saccharomyces cerevisiae Proteins / chemistry,  metabolism
Structure-Activity Relationship
ran GTP-Binding Protein / chemistry,  metabolism
Chemical
Reg. No./Substance:
0/CSE1 protein, S cerevisiae; 0/Multiprotein Complexes; 0/Nuclear Pore Complex Proteins; 0/Nuclear Proteins; 0/Nucleocytoplasmic Transport Proteins; 0/Saccharomyces cerevisiae Proteins; 86-01-1/Guanosine Triphosphate; EC 3.6.5.2/ran GTP-Binding Protein
Comments/Corrections
Comment In:
Nature. 2004 Dec 16;432(7019):815-6   [PMID:  15602540 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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