Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase

  1. Anna L Mallam
  2. David J Sidote
  3. Alan M Lambowitz  Is a corresponding author
  1. University of Texas at Austin, United States

Abstract

How different helicase families with a conserved catalytic 'helicase core' evolved to function on varied RNA and DNA substrates by diverse mechanisms remains unclear. Here, we used Mss116, a yeast DEAD-box protein that utilizes ATP to locally unwind dsRNA, to investigate helicase specificity and mechanism. Our results define the molecular basis for the substrate specificity of a DEAD-box protein. Additionally, they show that Mss116 has ambiguous substrate-binding properties and interacts with all four NTPs and both RNA and DNA. The efficiency of unwinding correlates with the stability of the 'closed-state' helicase core, a complex with nucleotide and nucleic acid that forms as duplexes are unwound. Crystal structures reveal that core stability is modulated by family-specific interactions that favor certain substrates. This suggests how present-day helicases diversified from an ancestral core with broad specificity by retaining core closure as a common catalytic mechanism while optimizing substrate-binding interactions for different cellular functions.

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Author details

  1. Anna L Mallam

    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. David J Sidote

    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alan M Lambowitz

    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    For correspondence
    lambowitz@austin.utexas.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2014, Mallam 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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  1. Anna L Mallam
  2. David J Sidote
  3. Alan M Lambowitz
(2014)
Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase
eLife 3:e04630.
https://doi.org/10.7554/eLife.04630

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https://doi.org/10.7554/eLife.04630