LOCAL HELIX CONTENT AND RNA-BINDING ACTIVITY OF THE N-TERMINAL LEUCINE-REPEAT REGION OF HEPATITIS-DELTA ANTIGEN

Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B vi rus (HBV) which provides the surface antigen for the viral coat. Our r esults show that the N-terminal leucine-repeat region of hepatitis del ta 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 H-1 NMR and circular d ichroism techniques is found to be an alpha-helix. The local helix con tent of this peptide was analyzed by NOEs and coupling constants. Muta genesis studies indicate that Lys(38), Lys(39), and Lys(40) within thi s alpha-helical peptide may be directly involved in RNA binding. A str uctural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for understanding its role in the interact ion with RNA.