Reversible Inhibition of the Fusion Activity of Measles Virus F Protein by an Engineered Intersubunit Disulfide Bridge
- 15 August 2007
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (16) , 8821-8826
- https://doi.org/10.1128/jvi.00754-07
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopyProceedings of the National Academy of Sciences, 2006
- Nonpeptide Inhibitors of Measles Virus EntryJournal of Medicinal Chemistry, 2006
- Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformationNature, 2006
- Design of a Small-Molecule Entry Inhibitor with Activity against Primary Measles Virus StrainsAntimicrobial Agents and Chemotherapy, 2005
- Multiple sequence alignment with the Clustal series of programsNucleic Acids Research, 2003
- Mutations in the Putative HR-C Region of the Measles Virus F 2 Glycoprotein Modulate Syncytium FormationJournal of Virology, 2003
- Measles Virus Envelope Glycoproteins Hetero-oligomerize in the Endoplasmic ReticulumJournal of Biological Chemistry, 2001
- Non‐replicating vaccinia vector efficiently expresses bacteriophage T7 RNA polymeraseFEBS Letters, 1995
- Introduction of intersubunit disulfide bonds in the membrane-distal region of the influenza hemagglutinin abolishes membrane fusion activityCell, 1992
- Semianalytical treatment of solvation for molecular mechanics and dynamicsJournal of the American Chemical Society, 1990