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Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19

Napetschnig, Johanna and Kassube, Susanne A. and Debler, Erik W. and Wong, Richard W. and Blobel, Günter and Hoelz, André (2009) Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19. Proceedings of the National Academy of Sciences of the United States of America, 106 (9). pp. 3089-3094. ISSN 0027-8424. PMCID PMC2651337.

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Key steps in the export of mRNA from the nucleus to the cytoplasm are the transport through the nuclear pore complex (NPC) and the subsequent remodeling of messenger RNA-protein (mRNP) complexes that occurs at the cytoplasmic side of the NPC. Crucial for these events is the recruitment of the DEAD-box helicase Ddx19 to the cytoplasmic filaments of the NPC that is mediated by the nucleoporin Nup214. Here, we present the crystal structure of the Nup214 N-terminal domain in complex with Ddx19 in its ADP-bound state at 2.5 Å resolution. Strikingly, the interaction surfaces are not only evolutionarily conserved but also exhibit strongly opposing surface potentials, with the helicase surface being positively and the Nup214 surface being negatively charged. We speculate that the positively charged surface of the interacting ADP-helicase binds competitively to a segment of mRNA of a linearized mRNP, passing through the NPC on its way to the cytoplasm. As a result, the ADP-helicase would dissociate from Nup214 and replace a single bound protein from the mRNA. One cycle of protein replacement would be accompanied, cooperatively, by nucleotide exchange, ATP hydrolysis, release of the ADP-helicase from mRNA and its rebinding to Nup214. Repeat of these cycles would remove proteins from a mRNP, one at a time, akin to a ratchet mechanism for mRNA export.

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URLURL TypeDescription Information CentralArticle
Hoelz, André0000-0003-1726-0127
Additional Information:© 2009 National Academy of Sciences. Contributed by Günter Blobel, December 29, 2008 (sent for review December 9, 2008). We thank Daniel Andor, Martin Kampmann, Vivien Nagy, Alina Patke, Hang Shi, and Pete Stavropoulos for discussions and comments on the manuscript; D. King for mass spectrometry analysis; Stephanie Etherton for help with editing the manuscript; and Corie Ralston and the staff at beamlines 8.2.1 and 8.2.2 of the Advanced Light Source for support during data collection. The peptide array was synthesized by the Protein Center of the Rockefeller University. E.W.D. is a Dale F. and Betty Ann Frey Fellow of the Damon Runyon Cancer Research Foundation. A.H. is supported by a grant from the Leukemia and Lymphoma Society. Author contributions: J.N. and A.H. designed research; J.N., S.A.K., E.W.D., R.W.W., and A.H. performed research; J.N., G.B., and A.H. analyzed data; and J.N., G.B., and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, (PDB ID codes 3FMO and 3FMP). This article contains supporting information online at
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationUNSPECIFIED
Leukemia and Lymphoma SocietyUNSPECIFIED
Subject Keywords:crystal structure; immunofluorescence localization; mRNA export; mutagenesis; Nup214-helicase complex
Issue or Number:9
PubMed Central ID:PMC2651337
Record Number:CaltechAUTHORS:20200407-091724460
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Official Citation:Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19. Johanna Napetschnig, Susanne A. Kassube, Erik W. Debler, Richard W. Wong, Günter Blobel, André Hoelz. Proceedings of the National Academy of Sciences Mar 2009, 106 (9) 3089-3094; DOI: 10.1073/pnas.0813267106
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102375
Deposited By: Tony Diaz
Deposited On:07 Apr 2020 17:57
Last Modified:07 Apr 2020 17:57

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