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Cell Rep. 2015 Oct 27;13(4):690-702. doi: 10.1016/j.celrep.2015.09.042. Epub 2015 Oct 17.

Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export.

Author information

1
Department of Molecular Biology, Faculty of Medicine, GZMB, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
2
Department of Molecular Structural Biology, Institute for Microbiology and Genetics, GZMB, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
3
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Bioanalytics, Institute for Clinical Chemistry, University Medical Center, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
4
Department of Molecular Structural Biology, Institute for Microbiology and Genetics, GZMB, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany. Electronic address: rficner@uni-goettingen.de.
5
Department of Molecular Biology, Faculty of Medicine, GZMB, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. Electronic address: rkehlen@gwdg.de.

Abstract

CRM1 is the major nuclear export receptor. During translocation through the nuclear pore, transport complexes transiently interact with phenylalanine-glycine (FG) repeats of multiple nucleoporins. On the cytoplasmic side of the nuclear pore, CRM1 tightly interacts with the nucleoporin Nup214. Here, we present the crystal structure of a 117-amino-acid FG-repeat-containing fragment of Nup214, in complex with CRM1, Snurportin 1, and RanGTP at 2.85 Å resolution. The structure reveals eight binding sites for Nup214 FG motifs on CRM1, with intervening stretches that are loosely attached to the transport receptor. Nup214 binds to N- and C-terminal regions of CRM1, thereby clamping CRM1 in a closed conformation and stabilizing the export complex. The role of conserved hydrophobic pockets for the recognition of FG motifs was analyzed in biochemical and cell-based assays. Comparative studies with RanBP3 and Nup62 shed light on specificities of CRM1-nucleoporin binding, which serves as a paradigm for transport receptor-nucleoporin interactions.

PMID:
26489467
DOI:
10.1016/j.celrep.2015.09.042
[Indexed for MEDLINE]
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