@article {322,
	title = {Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p.},
	journal = {Nature},
	volume = {490},
	number = {7418},
	year = {2012},
	month = {2012 Oct 4},
	pages = {121-5},
	abstract = {DEAD-box proteins are the largest family of nucleic acid helicases, and are crucial to RNA metabolism throughout all domains of life. They contain a conserved {\textquoteright}helicase core{\textquoteright} of two RecA-like domains (domains (D)1 and D2), which uses ATP to catalyse the unwinding of short RNA duplexes by non-processive, local strand separation. This mode of action differs from that of translocating helicases and allows DEAD-box proteins to remodel large RNAs and RNA-protein complexes without globally disrupting RNA structure. However, the structural basis for this distinctive mode of RNA unwinding remains unclear. Here, structural, biochemical and genetic analyses of the yeast DEAD-box protein Mss116p indicate that the helicase core domains have modular functions that enable a novel mechanism for RNA-duplex recognition and unwinding. By investigating D1 and D2 individually and together, we find that D1 acts as an ATP-binding domain and D2 functions as an RNA-duplex recognition domain. D2 contains a nucleic-acid-binding pocket that is formed by conserved DEAD-box protein sequence motifs and accommodates A-form but not B-form duplexes, providing a basis for RNA substrate specificity. Upon a conformational change in which the two core domains join to form a {\textquoteright}closed state{\textquoteright} with an ATPase active site, conserved motifs in D1 promote the unwinding of duplex substrates bound to D2 by excluding one RNA strand and bending the other. Our results provide a comprehensive structural model for how DEAD-box proteins recognize and unwind RNA duplexes. This model explains key features of DEAD-box protein function and affords a new perspective on how the evolutionarily related cores of other RNA and DNA helicases diverged to use different mechanisms.},
	keywords = {Adenosine Triphosphatases, Adenosine Triphosphate, Amino Acid Motifs, Base Sequence, Catalytic Domain, Conserved Sequence, Crystallography, X-Ray, DEAD-box RNA Helicases, Evolution, Molecular, GC Rich Sequence, Models, Molecular, Nucleic Acid Conformation, Protein Structure, Tertiary, RNA, Double-Stranded, RNA-Binding Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship, Substrate Specificity},
	issn = {1476-4687},
	doi = {10.1038/nature11402},
	author = {Mallam, Anna L and Del Campo, Mark and Gilman, Benjamin and Sidote, David J and Lambowitz, Alan M}
}
