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Mutational analysis of the candidate internal fusion peptide of the avian leukosis and sarcoma virus subgroup A envelope glycoprotein.

Abstract
The transmembrane subunit (TM) of the avian leukosis and sarcoma virus (ALSV) envelope glycoprotein (Env) contains a stretch of conserved hydrophobic amino acids internal to its amino terminus (residues 21 to 42). By analogy with similar sequences in other viral envelope glycoproteins, this region has been proposed to be a fusion peptide. We investigated the role of this region by changing each of three hydrophobic residues (Ile-21, Val-30, and Ile-39) to glutamatic acid and lysine in the ALSV subgroup A Env. Like wild-type (wt) Env, all six mutant Env proteins were proteolytically processed, oligomerized, and expressed at the cell surface in a form that bound Tva, the ALSV subgroup A receptor. Like wt Env, Ile21Glu, Ile21Lys, Va30Glu, and Val30Lys changed conformation upon binding Tva, as assayed by sensitivity to thermolysin. Ile39Glu and Ile39Lys were cleaved by thermolysin in both the absence and presence of Tva. Although incorporated into virus particles at approximately equal levels, all mutant Envs were compromised in their ability to support infection. The mutants at residues 21 and 30 showed levels of infection 2 to 3 orders of magnitude lower than that of wt Env. The mutants at residue 39 were noninfectious. Furthermore, none of the mutants displayed activity in a cell-cell fusion assay. Our results support the contention that residues 21 to 42 of ALSV subgroup A Env constitute its fusion peptide.
AuthorsL D Hernandez, J M White
JournalJournal of virology (J Virol) Vol. 72 Issue 4 Pg. 3259-67 (Apr 1998) ISSN: 0022-538X [Print] United States
PMID9525653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Avian Proteins
  • Glycoproteins
  • Receptors, Virus
  • Tva receptor
  • Viral Fusion Proteins
Topics
  • 3T3 Cells
  • Alpharetrovirus (genetics, metabolism)
  • Amino Acid Sequence
  • Animals
  • Avian Proteins
  • Cell Fusion
  • Cell Line, Transformed
  • Glycoproteins (chemistry, genetics, metabolism)
  • Membrane Fusion
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Rabbits
  • Receptors, Virus (metabolism)
  • Viral Fusion Proteins (chemistry, genetics, metabolism)

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