Structural and mechanistic aspect of DEAD-box helicases

Abstract

DFAD-box helicases are ubiquitous enzymes that catalyze the unwinding of energetically stable duplex DNA (DNA helicases) or duplex RNA secondary structures (RNA helicases). DNA helicases are involved in replication, repair, recombination, and transcription, while the DEAD-box RNA helicases are involved in modulation of RNA structure and thereby influence RNA synthesis, splicing, replication, translation initiation, editing, rRNA processing, ribosome assembly, nuclear mRNA export, mRNA stabilization and degradation. They are associated with intrinsic ssDNA-dependent or RNA-dependent ATPase activities, which provide the energy for the helicase action. Mechanistically, there are two classes of helicases, those that can translocate 3'- to 5'-, or 5' to 3' directions with respect to the strand on which they initially bind. A hallmark of most of the helicases (but not for all) is the existence of a set of nine highly conserved amino acid sequences called 'helicase motifs', which are clustered together for helicase function. One of the important helicase motifs is DEAD (Asp-Glu-Ala-Asp) that is why the family of these proteins is called DEAD-box helicases. PcrA helicase from Bacillius stearothermophilus was the first helicase whose crystal structure was solved in 1996 by an Indian scientist H. S. Subramanya in Dale B. Wigley's group at University of Oxford, UK. After this several DEAD-box helicases have been crystallized and suggested a common structural fold for their function. Furthermore, the information on the function of conserved helicase motifs and mechanism of DNA or RNA unwinding is also emerging. In this article we have covered possibly all the helicases whose structure have been solved and the possible mechanisms of unwinding.