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

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. In this study, 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.

journal_name

Elife

journal_title

eLife

authors

Mallam AL,Sidote DJ,Lambowitz AM

doi

10.7554/eLife.04630

subject

Has Abstract

pub_date

2014-12-12 00:00:00

pages

e04630

issn

2050-084X

journal_volume

3

pub_type

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