CRYSTAL-STRUCTURE OF RNA HELICASE FROM GENOTYPE 1B HEPATITIS-C VIRUS - A FEASIBLE MECHANISM OF UNWINDING DUPLEX RNA

Crystal structure of RNA helicase domain from genotype 1b hepatitis C virus has been determined at 2.3 Angstrom resolution by the multiple i somorphous replacement method. The structure consists of three domains that form a Y-shaped molecule. One is a NTPase domain containing two highly conserved NTP binding motifs. Another is an RNA binding domain containing a conserved RNA binding motif. The third is a helical domai n that contains no beta-strand. The RNA binding domain of the molecule is distinctively separated from the other two domains forming an inte rdomain cleft into which single stranded RNA can be modeled. A channel is found between a pair of symmetry-related molecules which exhibit t he most extensive crystal packing interactions. A stretch of single st randed RNA can be modeled with electrostatic complementarity into the interdomain cleft and continuously through the channel. These observat ions suggest that some form of this dimer is likely to be the function al form that unwinds double stranded RNA processively by passing one s trand of RNA through the channel and passing the other strand outside of the dimer. A ''descending molecular see-saw'' model is proposed tha t is consistent with directionality of unwinding and other physicochem ical properties of RNA helicases.