Solution Structure of an N-Capping Peptide from the N-terminal Leucine-Repeat Region of Hepatitis Delta Antigen

Abstract

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 δ 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 α-helical conformation in TFE-containing solution. However, it exhibited low α-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 (dAgCap24–38am) was synthesized and, surprisingly, its solution structure was found to be a stable α-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.