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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-6-16
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pubmed:databankReference |
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pubmed:abstractText |
The karyopherin CRM1 mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES). To elucidate the precise mechanism by which NES-cargos are dissociated from CRM1 in the cytoplasm, which is important for transport directionality, we determined a 2.0-A resolution crystal structure of yeast CRM1:RanBP1:RanGTP complex, an intermediate in the disassembly of the CRM1 nuclear export complex. The structure shows that on association of Ran-binding domain (RanBD) of RanBP1 with CRM1:NES-cargo:RanGTP complex, RanBD and the C-terminal acidic tail of Ran induce a large movement of the intra-HEAT9 loop of CRM1. The loop moves to the CRM1 inner surface immediately behind the NES-binding site and causes conformational rearrangements in HEAT repeats 11 and 12 so that the hydrophobic NES-binding cleft on the CRM1 outer surface closes, squeezing out the NES-cargo. This allosteric mechanism accelerates dissociation of NES by over two orders of magnitude. Structure-based mutagenesis indicated that the HEAT9 loop also functions as an allosteric autoinhibitor to stabilize CRM1 in a conformation that is unable to bind NES-cargo in the absence of RanGTP.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20485264-10078529,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20485264-9774653
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1460-2075
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2002-13
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20485264-Active Transport, Cell Nucleus,
pubmed-meshheading:20485264-Allosteric Regulation,
pubmed-meshheading:20485264-Crystallography, X-Ray,
pubmed-meshheading:20485264-Guanosine Triphosphate,
pubmed-meshheading:20485264-Karyopherins,
pubmed-meshheading:20485264-Models, Molecular,
pubmed-meshheading:20485264-Mutagenesis, Site-Directed,
pubmed-meshheading:20485264-Nuclear Proteins,
pubmed-meshheading:20485264-Protein Binding,
pubmed-meshheading:20485264-Protein Structure, Quaternary,
pubmed-meshheading:20485264-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:20485264-Saccharomyces cerevisiae
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pubmed:year |
2010
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pubmed:articleTitle |
An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1.
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pubmed:affiliation |
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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