Crystal Structure of RNA Helicase from Genotype 1b Hepatitis C Virus

Abstract

Crystal structure of RNA helicase domain from geno-type 1b hepatitis C virus has been determined at 2.3 Å resolution by the multiple isomorphous replacement method. The structure consists of three domains that form a Y-shaped molecule. One is a NTPase domain con-taining two highly conserved NTP binding motifs. An-other is an RNA binding domain containing a conserved RNA binding motif. The third is a helical domain that contains no ␤-strand. The RNA binding domain of the molecule is distinctively separated from the other two domains forming an interdomain cleft into which single stranded RNA can be modeled. A channel is found be-tween a pair of symmetry-related molecules which ex-hibit the most extensive crystal packing interactions. A stretch of single stranded RNA can be modeled with electrostatic complementarity into the interdomain cleft and continuously through the channel. These observa-tions suggest that some form of this dimer is likely to be the functional form that unwinds double stranded RNA processively by passing one strand of RNA through the channel and passing the other strand outside of the dimer. A " descending molecular see-saw " model is pro-posed that is consistent with directionality of unwinding and other physicochemical properties of RNA helicases.