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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2004-12-2
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pubmed:databankReference |
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pubmed:abstractText |
CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase Ran. We present a structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy. The architecture of CRM1 resembles that of the import receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran binding. Residues critical for NES recognition are identified adjacent to the cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We present evidence that a conformational change of the Ran binding loop accounts for the cooperativity of Ran- and substrate binding and for the selective enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate that a single architectural and mechanistic framework can explain the divergent effects of RanGTP on substrate binding by many import and export receptors.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Karyopherins,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/TNPO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/beta Karyopherins,
http://linkedlifedata.com/resource/pubmed/chemical/exportin 1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/leptomycin B,
http://linkedlifedata.com/resource/pubmed/chemical/ran GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
761-75
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15574331-Active Transport, Cell Nucleus,
pubmed-meshheading:15574331-Amino Acid Sequence,
pubmed-meshheading:15574331-Binding Sites,
pubmed-meshheading:15574331-Cell Nucleus,
pubmed-meshheading:15574331-Crystallography, X-Ray,
pubmed-meshheading:15574331-Dose-Response Relationship, Drug,
pubmed-meshheading:15574331-Fatty Acids, Unsaturated,
pubmed-meshheading:15574331-GTP Phosphohydrolases,
pubmed-meshheading:15574331-Guanosine Triphosphate,
pubmed-meshheading:15574331-Humans,
pubmed-meshheading:15574331-Image Processing, Computer-Assisted,
pubmed-meshheading:15574331-Karyopherins,
pubmed-meshheading:15574331-Leucine,
pubmed-meshheading:15574331-Microscopy, Electron,
pubmed-meshheading:15574331-Models, Biological,
pubmed-meshheading:15574331-Models, Molecular,
pubmed-meshheading:15574331-Molecular Sequence Data,
pubmed-meshheading:15574331-Protein Binding,
pubmed-meshheading:15574331-Protein Conformation,
pubmed-meshheading:15574331-Protein Structure, Secondary,
pubmed-meshheading:15574331-Protein Structure, Tertiary,
pubmed-meshheading:15574331-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15574331-Sequence Homology, Amino Acid,
pubmed-meshheading:15574331-beta Karyopherins,
pubmed-meshheading:15574331-ran GTP-Binding Protein
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pubmed:year |
2004
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pubmed:articleTitle |
Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.
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pubmed:affiliation |
European Molecular Biology Laboratory, Grenoble Outstation, B.P. 181, 38042 Grenoble Cedex 9, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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