title: The mechanism of ATP-dependent RNA unwinding by DEAD box proteins.
abstract: DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA (dsRNA). In addition, they facilitate protein displacement and remodeling of RNA or RNA/protein complexes. Their hallmark feature is local destabilization of RNA duplexes. Here, we summarize current data on the DEAD box protein mechanism and present a model for RNA unwinding that integrates recent data on the effect of ATP analogs and mutations on DEAD box protein activity. DEAD box proteins share a conserved helicase core with two flexibly linked RecA-like domains that contain all helicase signature motifs. Variable flanking regions contribute to substrate binding and modulate activity. In the presence of ATP and RNA, the helicase core adopts a compact, closed conformation with extensive interdomain contacts and high affinity for RNA. In the closed conformation, the RecA-like domains form a catalytic site for ATP hydrolysis and a continuous RNA binding site. A kink in the backbone of the bound RNA locally destabilizes the duplex. Rearrangement of this initial complex generates a hydrolysis- and unwinding-competent state. From this complex, the first RNA strand can dissociate. After ATP hydrolysis and phosphate release, the DEAD box protein returns to a low-affinity state for RNA. Dissociation of the second RNA strand and reopening of the cleft in the helicase core allow for further catalytic cycles.
authors.affiliation: Biozentrum, Biophysical Chemistry, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hilbert
authors.forename: Anne R
authors.initials: AR
authors.lastname: Karow
authors.forename: Dagmar
authors.initials: D
authors.lastname: Klostermeier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D012330:RNA, Double-Stranded; D000255:Adenosine Triphosphate; D053487:DEAD-box RNA Helicases