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Published June 8, 2010 | Published + Supplemental Material
Journal Article Open

Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1


The export of mRNAs is a multistep process, involving the packaging of mRNAs into messenger ribonucleoprotein particles (mRNPs), their transport through nuclear pore complexes, and mRNP remodeling events prior to translation. Ribonucleic acid export 1 (Rae1) and Nup98 are evolutionarily conserved mRNA export factors that are targeted by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. Here, we present the crystal structure of human Rae1 in complex with the Gle2-binding sequence (GLEBS) of Nup98 at 1.65 Å resolution. Rae1 forms a seven-bladed β-propeller with several extensive surface loops. The Nup98 GLEBS motif forms an ≈50-Å-long hairpin that binds with its C-terminal arm to an essentially invariant hydrophobic surface that extends over the entire top face of the Rae1 β-propeller. The C-terminal arm of the GLEBS hairpin is necessary and sufficient for Rae1 binding, and we identify a tandem glutamate element in this arm as critical for complex formation. The Rae1•Nup98^(GLEBS) surface features an additional conserved patch with a positive electrostatic potential, and we demonstrate that the complex possesses single-stranded RNA-binding capability. Together, these data suggest that the Rae1•Nup98 complex directly binds to the mRNP at several stages of the mRNA export pathway.

Additional Information

© 2010 National Academy of Sciences. Contributed by Günter Blobel, May 3, 2010 (sent for review April 2, 2010). We thank Erik Debler, Vivien Nagy, Johanna Napetschnig, Alina Patke, Deniz Top, Pete Stavropoulos, and Kimihisa Yoshida for critical reading of the manuscript, and Stephanie Etherton for help with editing the manuscript. Analytical ultracentrifugation was carried out by the Wadsworth Center Biochemistry Core Facility. In addition, we thank Erik Debler for help and Nagarajan Venugopalan (GM/CA-CAT) for support during data collection. A.H. was supported by a grant from the Leukemia and Lymphoma Society. Author contributions: Y.R., H.-S.S., and A.H. designed research; Y.R., H.-S.S., and A.H. performed research; Y.R., H.-S.S., and A.H. analyzed data; Y.R., H.-S.S., G.B., and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 3MMY). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1005389107/-/DCSupplemental.

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Published - 10406.full.pdf

Supplemental Material - pnas.1005389107_SI.pdf


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