Abstract
Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. Our results show that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg), encompassing residues 24-50, binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. The solution conformation of a synthetic peptide corresponding to residues 24-50 of HDAg as determined by two-dimensional 1 H NMR and circular dichroism techniques is found to be an α-helix. The local helix content of this peptide was analyzed by NOEs and coupling constants. Mutagenesis studies indicate that Lys 38 , Lys 39 , and Lys 40 within this α-helical peptide may be directly involved in RNA binding. A structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for understanding its role in the interaction with RNA.