Skip to main content

The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells.

Publication ,  Journal Article
Otto, JC; Casey, PJ
Published in: J Biol Chem
March 1, 1996

The hepatitis delta virus large antigen (lHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. Although the presence of the Gln as the COOH-terminal residue generally specifies addition of the 15-carbon farnesyl isoprenoid, earlier reports had suggested that the protein is modified by the 20-carbon geranylgeranyl. The prenylation of lHDAg was examined in vitro using a fusion protein between glutathione S-transferase and the COOH-terminal 117 amino acids of lHDAg (GST-lHDAg). When recombinant GST-lHDAg was incubated with bovine brain cytosol in the presence of either farnesyl diphosphate or geranylgeranyl diphosphate, GST-lHDAg was preferentially farnesylated. Geranylgeranylation of the fusion protein was also observed, although at a rate considerably less than that of farnesylation. Using purified recombinant protein prenyltransferases, GST-lHDAg was found to be an excellent substrate (apparent Km = 0.8 microM) for protein farnesyltransferase (FTase), while modification by protein geranylgeranyltransferase I (GGTase I) was not detected. FTase was also able to catalyze geranylgeranylation of GST-lHDAg at a very low rate, suggesting that the low level of geranylgeranylation of GST-lHDAg observed in cytosolic preparations was mediated by FTase. Consistent with our observations on the in vitro prenylation of the GST-lHDAg fusion protein, isoprenoid analysis of authentic lHDAg expressed in COS cells demonstrated that the protein was farnesylated. Geranylgeranylation of lHDAg expressed in COS cells was not observed. As prenylation of lHDAg is required for the assembly of the hepatitis delta viral particle, these results suggest that inhibitors of FTase may be useful therapeutic agents for treatment of delta virus infection.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 1, 1996

Volume

271

Issue

9

Start / End Page

4569 / 4572

Location

United States

Related Subject Headings

  • Transfection
  • Spodoptera
  • Sesquiterpenes
  • Recombinant Fusion Proteins
  • Protein Prenylation
  • Polyisoprenyl Phosphates
  • Molecular Sequence Data
  • Kinetics
  • Hepatitis delta Antigens
  • Hepatitis Delta Virus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Otto, J. C., & Casey, P. J. (1996). The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells. J Biol Chem, 271(9), 4569–4572. https://doi.org/10.1074/jbc.271.9.4569
Otto, J. C., and P. J. Casey. “The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells.J Biol Chem 271, no. 9 (March 1, 1996): 4569–72. https://doi.org/10.1074/jbc.271.9.4569.
Otto JC, Casey PJ. The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells. J Biol Chem. 1996 Mar 1;271(9):4569–72.
Otto, J. C., and P. J. Casey. “The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells.J Biol Chem, vol. 271, no. 9, Mar. 1996, pp. 4569–72. Pubmed, doi:10.1074/jbc.271.9.4569.
Otto JC, Casey PJ. The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells. J Biol Chem. 1996 Mar 1;271(9):4569–4572.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 1, 1996

Volume

271

Issue

9

Start / End Page

4569 / 4572

Location

United States

Related Subject Headings

  • Transfection
  • Spodoptera
  • Sesquiterpenes
  • Recombinant Fusion Proteins
  • Protein Prenylation
  • Polyisoprenyl Phosphates
  • Molecular Sequence Data
  • Kinetics
  • Hepatitis delta Antigens
  • Hepatitis Delta Virus