1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Structural insights into the mechanism of the DEAH-box RNA helicase Prp43

  1. Marcel J Tauchert
  2. Jean-Baptiste Fourmann
  3. Reinhard Lührmann
  4. Ralf Ficner  Is a corresponding author
  1. Georg-August-University Göttingen, Germany
  2. Max Planck Institute for Biophysical Chemistry, Germany
Research Article
  • Cited 47
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Cite this article as: eLife 2017;6:e21510 doi: 10.7554/eLife.21510

Abstract

The DEAH-box helicase Prp43 is a key player in pre-mRNA splicing as well as the maturation of rRNAs. The exact modus operandi of Prp43 and of all other spliceosomal DEAH-box RNA helicases is still elusive. Here, we report crystal structures of Prp43 complexes in different functional states and the analysis of structure-based mutants providing insights into the unwinding and loading mechanism of RNAs. The Prp43•ATP-analog•RNA complex shows the localization of the RNA inside a tunnel formed by the two RecA-like and C-terminal domains. In the ATP-bound state this tunnel can be transformed into a groove prone for RNA binding by large rearrangements of the C-terminal domains. Several conformational changes between the ATP- and ADP-bound states explain the coupling of ATP hydrolysis to RNA translocation, mainly mediated by a β-turn of the RecA1 domain containing the newly identified RF motif. This mechanism is clearly different to those of other RNA helicases.

Data availability

The following data sets were generated
The following previously published data sets were used
    1. Prabu JR
    2. Conti E
    (2015) Structure of MLE RNA ADP AlF4 complex
    Publicly available at the RCSB Protein Data Bank (accession no: 5AOR).

Article and author information

Author details

  1. Marcel J Tauchert

    Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Jean-Baptiste Fourmann

    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Reinhard Lührmann

    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6403-4432
  4. Ralf Ficner

    Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August-University Göttingen, Göttingen, Germany
    For correspondence
    rficner@uni-goettingen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1739-6086

Funding

Deutsche Forschungsgemeinschaft ((SFB860 TPA2))

  • Ralf Ficner

Deutsche Forschungsgemeinschaft ((SFB860 TPA1))

  • Reinhard Lührmann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

  1. Received: September 14, 2016
  2. Accepted: January 15, 2017
  3. Accepted Manuscript published: January 16, 2017 (version 1)
  4. Version of Record published: January 24, 2017 (version 2)

Copyright

© 2017, Tauchert et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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