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 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 1H NMR and circular dichroism techniques is found to be an alpha-helix. The local helix content of this peptide was analyzed by NOEs and coupling constants. Mutagenesis studies indicate that Lys38, Lys39, and Lys40 within this alpha-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.
Cheng
J W
JW
Department of Life Science, National Tsing Hua University, Taiwan, Republic of China.
Lin
I J
IJ
Lou
Y C
YC
Pai
M T
MT
Wu
H N
HN
D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004279:DNA, Viral / Q000737:chemistry* / Q000378:metabolism*; D018963:Hepatitis Antigens / Q000737:chemistry* / Q000378:metabolism*; D003698:Hepatitis Delta Virus / Q000235:genetics* / Q000378:metabolism; D035923:Hepatitis delta Antigens; D006859:Hydrogen; D007930:Leucine; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary
D004279:DNA, Viral; D018963:Hepatitis Antigens; D035923:Hepatitis delta Antigens; D010446:Peptide Fragments; C442244:hepatitis delta virus large antigen; D006859:Hydrogen; D007930:Leucine