title: The DEXD/H-box RNA helicase DDX19 is regulated by an {alpha}-helical switch.
abstract: DEXD/H-box RNA helicases couple ATP hydrolysis to RNA remodeling by an unknown mechanism. We used x-ray crystallography and biochemical analysis of the human DEXD/H-box protein DDX19 to investigate its regulatory mechanism. The crystal structures of DDX19, in its RNA-bound prehydrolysis and free posthydrolysis state, reveal an alpha-helix that inserts between the conserved domains of the free protein to negatively regulate ATPase activity. This finding was corroborated by biochemical data that confirm an autoregulatory function of the N-terminal region of the protein. This is the first study describing crystal structures of a DEXD/H-box protein in its open and closed cleft conformations.
authors.affiliation: Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-17177 Stockholm, Sweden.
authors.forename: Ruairi
authors.initials: R
authors.lastname: Collins
authors.forename: Tobias
authors.initials: T
authors.lastname: Karlberg
authors.forename: Lari
authors.initials: L
authors.lastname: Lehtiö
authors.forename: Patrick
authors.initials: P
authors.lastname: Schütz
authors.forename: Susanne
authors.initials: S
authors.lastname: van den Berg
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Dahlgren
authors.forename: Martin
authors.initials: M
authors.lastname: Hammarström
authors.forename: Johan
authors.initials: J
authors.lastname: Weigelt
authors.forename: Herwig
authors.initials: H
authors.lastname: Schüler
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D029543:Nucleocytoplasmic Transport Proteins; C121148:DDX19B protein, human; D053487:DEAD-box RNA Helicases