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.