Solution structure of an N-capping peptide from 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. The RNA genome of HDV encodes two proteins, the small delta antigen and the large delta antigen, which differ only with the latter having an additional 19 amino acids at the C-terminus. Previously, we have shown that dAg24-50, a synthetic peptide corresponding to residues 24-50 of the N-terminal leucine-repeat region of hepatitis delta antigen, binds to the viral RNA and forms an alpha-helical conformation in TFE-containing solution. However, it exhibited low alpha-helicity (less than 5%) in the absence of TFE. In order to obtain biologically active delta antigen peptides with higher structural stability in solution, an N-capping 21-residue polypeptide corresponding to residues 24-38 of hepatitis delta antigen (dAg(Cap24-38am)) was synthesized and, surprisingly, its solution structure was found to be a stable alpha-helix (64%) by circular dichroism and 1H NMR techniques. Moreover, the structure of the capping box shows the characteristic L-shaped bend perpendicular to the helix axis. This structural knowledge provides a molecular basis for understanding the role of the N-terminal leucine-repeat region of hepatitis delta antigen and has a significant potential for the development of diagnostic and therapeutic methods for HDV.
Lou
Y C
YC
Department of Life Science, National Tsing Hua University, Taiwan, Republic of China.
Lin
I J
IJ
Pai
M T
MT
Cheng
J W
JW
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018963:Hepatitis Antigens / Q000737:chemistry*; D003698:Hepatitis Delta Virus / Q000737:chemistry*; D035923:Hepatitis delta Antigens; D007930:Leucine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018963:Hepatitis Antigens; D035923:Hepatitis delta Antigens; D010455:Peptides; C442244:hepatitis delta virus large antigen; D007930:Leucine