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PMID: 19219046 Published · ppublish English Journal Article

The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner.

Nature structural & molecular biology ·Vol. 16 ·No. 3 ·2009-03-00 ·Pages 247-54

von Moeller H, Basquin C, Conti E

Abstract

The DEAD-box protein DBP5 is essential for mRNA export in both yeast and humans. It binds RNA and is concentrated and locally activated at the cytoplasmic side of the nuclear pore complex. We have determined the crystal structures of human DBP5 bound to RNA and AMPPNP, and bound to the cytoplasmic nucleoporin NUP214. The structures reveal that binding of DBP5 to nucleic acid and to NUP214 is mutually exclusive. Using in vitro assays, we demonstrate that NUP214 decreases both the RNA binding and ATPase activities of DBP5. The interactions are mediated by conserved residues, implying a conserved recognition mechanism. These results suggest a framework for the consecutive steps leading to the release of mRNA at the final stages of nuclear export. More generally, they provide a paradigm for how binding of regulators can specifically inhibit DEAD-box proteins.

MeSH Terms
Adenylyl Imidodiphosphate/chemistry,metabolism Crystallography, X-Ray DEAD-box RNA Helicases/chemistry,metabolism Humans Models, Molecular Nuclear Pore Complex Proteins/chemistry,metabolism Nucleocytoplasmic Transport Proteins/chemistry,metabolism Protein Binding Protein Structure, Quaternary RNA, Messenger/metabolism
Chemicals
NUP214 protein, human Nuclear Pore Complex Proteins Nucleocytoplasmic Transport Proteins RNA, Messenger Adenylyl Imidodiphosphate DDX19B protein, human DEAD-box RNA Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
von Moeller Holger
Max-Planck-Institute of Biochemistry, Department of Structural Cell Biology, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Basquin Claire
Conti Elena
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1561
Published
2009-03-00
Epub
2009-00-15
Pages
247-54
Language
English
Region
United States
NLM ID
101186374
Subset
IM
Databases
PDB
3FHC, 3FHT
External Links
PubMed source DOI: 10.1038/nsmb.1561 View journal details
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