title: Structure of the RNA Helicase MLE Reveals the Molecular Mechanisms for Uridine Specificity and RNA-ATP Coupling.
abstract: The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the Drosophila dosage compensation complex. We identified a stable MLE core comprising the DExH helicase module and two auxiliary domains: a dsRBD and an OB-like fold. MLEcore is an unusual DExH helicase that can unwind blunt-ended RNA duplexes and has specificity for uridine nucleotides. We determined the 2.1 Å resolution structure of MLEcore bound to a U10 RNA and ADP-AlF4. The OB-like and dsRBD folds bind the DExH module and contribute to form the entrance of the helicase channel. Four uridine nucleotides engage in base-specific interactions, rationalizing the conservation of uridine-rich sequences in critical roX substrates. roX2 binding is orchestrated by MLE's auxiliary domains, which is prerequisite for MLE localization to the male X chromosome. The structure visualizes a transition-state mimic of the reaction and suggests how eukaryotic DEAH/RHA helicases couple ATP hydrolysis to RNA translocation.
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: J Rajan
authors.initials: JR
authors.lastname: Prabu
authors.affiliation: Biomedical Center and Center for Integrated Protein Science, Ludwig-Maximilians-University, 82152 Martinsried, Germany.
authors.forename: Marisa
authors.initials: M
authors.lastname: Müller
authors.affiliation: Biomedical Center and Center for Integrated Protein Science, Ludwig-Maximilians-University, 82152 Martinsried, Germany.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Thomae
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schüssler
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Fabien
authors.initials: F
authors.lastname: Bonneau
authors.affiliation: Biomedical Center and Center for Integrated Protein Science, Ludwig-Maximilians-University, 82152 Martinsried, Germany. Electronic address: pbecker@med.uni-muenchen.de.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Becker
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany. Electronic address: conti@biochem.mpg.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D008297:Male; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C092595:Pabp2 protein, Drosophila; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C070837:mle protein, Drosophila; D012313:RNA; D000255:Adenosine Triphosphate; D004265:DNA Helicases; D020365:RNA Helicases
keywords: DEAH; MLE; dosage compensation; helicase; roX RNA; structure