Solution structure and RNA-binding activity of the n-terminal leucine-repeat region of hepatitis delta antigen
✍ Scribed by I-Jin Lin; Yuan-Chao Lou; Ming-Tao Pai; Huey-Nan Wu; Jya-Wei Cheng
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 205 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0887-3585
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✦ Synopsis
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. The two proteins resemble each other except for the presence of an additional 19 amino acids at the C terminus of the latter species. We have found that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg) binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. A 27-residue polypeptide corresponding to residues 24-50 of HDAg, designated dAg 24-50 , was synthesized, and its solution structure was found to be an ␣-helix by circular dichroism and 1 H-nuclear magnetic resonance (NMR) techniques. Binding affinity of dAg 24-50 with HDV genomic RNA was found to increase with its ␣-helical content, and it was further confirmed by modifying its N-and C-terminal groups. Furthermore, the absence of RNA binding activity in the mutant peptides, dAgM 24-50am and dAgM Ac24-50am , in which Lys38, Lys39, and Lys40 were changed to Glu, indicates a possible involvement of these residues in their binding activity. Structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for the understanding of its role in the interaction with RNA.