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Solution structure and RNA‐binding activity of the n‐terminal leucine‐repeat region of hepatitis delta antigen
Author(s) -
Lin IJin,
Lou YuanChao,
Pai MingTao,
Wu HueyNan,
Cheng JyaWei
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19991001)37:1<121::aid-prot12>3.0.co;2-t
Subject(s) - rna , leucine , microbiology and biotechnology , virus , antigen , n terminus , amino acid , chemistry , biology , hepatitis b virus , virology , biochemistry , peptide sequence , gene , genetics
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 α‐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 α‐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. Proteins 1999;37:121–129. © 1999 Wiley‐Liss, Inc.