Open AccessReversible Inhibition of the Fusion Activity of Measles Virus F Protein by an Engineered Intersubunit Disulfide Bridge
Author(s) -
Jin K. Lee,
Andrew Prussia,
James P. Snyder,
Richard K. Plemper
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00754-07
Subject(s) - dithiothreitol , trimer , measles virus , biology , disulfide bond , covalent bond , virus , paramyxoviridae , fusion protein , monomer , biophysics , mononegavirales , biochemistry , microbiology and biotechnology , virology , recombinant dna , chemistry , measles , enzyme , dimer , vaccination , organic chemistry , viral disease , gene , polymer
In search of target sites for the development of paramyxovirus inhibitors, we have engineered disulfide bridges to introduce covalent links into the prefusion F protein trimer of measles virus. F-Edm-452C/460C, predicted to bridge head and stalk domains of different F monomers, shows a high degree of proteolytic maturation and surface expression, predominantly as stable, dithiothreitol-sensitive trimers, but no fusion activity. Reduction of disulfide bridges partially restores activity. These findings underscore the importance of reversible intersubunit interactions between the stalk and head domains for F activity. Noncovalent small molecules mimicking this behavior may constitute a potent strategy for preventing paramyxovirus entry.