Putative reaction intermediates in Crm1-mediated nuclear protein export.
We discovered several novel interactions between proteins involved in Crm1-mediated nuclear export of the nuclear export signal containing human immunodeficiency virus type 1 protein Rev. First, a Rev/Crm1/RanGTP complex (where Ran is Ras-related nuclear protein) reacts with some nucleoporins (Nup42 and Nup159) but not others (NSP1, Nup116, and Nup1), forming a Nup/Crm1/RanGTP complex and concomitantly releasing Rev. Second, RanBP1 (or homologous proteins) can displace Nup and form a ternary RanBP1/RanGTP/Crm1 complex that can be disassembled by RanGAP via GTP hydrolysis. Third, and most surprisingly, RanBP1/RanGTP/Crm1 can be disassembled without GTP hydrolysis by the nucleotide exchange factor RanGEF. Recycling of a Ran/RanGEF complex by GTP and Mg2+ is stimulated by both Crm1 and Rev, allowing reformation of a Rev/Crm1/RanGTP complex. Based on these reactions we propose a model for Crm1-mediated export.
Floer
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M
Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA.
Blobel
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G
D001692:Biological Transport; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D015694:Gene Products, rev / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D006868:Hydrolysis; D028884:Karyopherins; D008565:Membrane Proteins / Q000378:metabolism; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D018272:Porins / Q000378:metabolism; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D005656:Fungal Proteins; D015694:Gene Products, rev; D006160:Guanosine Triphosphate; D028884:Karyopherins; D008565:Membrane Proteins; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D018272:Porins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C119724:AGFG1 protein, human; C062748:NSP1 protein, S cerevisiae; C077730:NUP116 protein, S cerevisiae; C093510:NUP159 protein, S cerevisiae