Structural and Functional Studies on the Human Dead-Box Helicase Ddx1

RNA helicases are essential in all steps of RNA maturation, beginning with transcription and ending with RNA decay. They catalyze the separation of nucleic acid double strands and thereby facilitate structural remodeling. Their cellular importance is reflected in severe diseases caused by RNA helicase dysregulation. The largest group of RNA helicases is confined by the so called DEAD-box helicases of superfamily 2, characterized by the signature sequence D-E-A-D. DEAD-box helicases share a structurally conserved core of two RecA-like domains that carry signature motifs involved in ATP-binding, ATP-hydrolysis, RNA-binding and RNA-remodeling. An exceptional member of the DEAD-box protein family is the human RNA helicase DDX1(DEAD-box helicase1). In contrast to all other family members, DDX1 harbors a SPRY domain insertion in between the signature motifs of the helicase core. DDX1 is involved in a plethora of different RNA maturation processes and has been associated with tumor progression. Moreover due to its versatile function in RNA processing, it is hijacked by viruses for their replication. This medical relevance makes DDX1 a potential target for the development of pharmaceutics.