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Journal of Virology, August 2007, p. 8821-8826, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00754-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Reversible Inhibition of the Fusion Activity of Measles Virus F Protein by an Engineered Intersubunit Disulfide Bridge{triangledown}

Jin K. Lee,1 Andrew Prussia,2 James P. Snyder,2 and Richard K. Plemper1*

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322,1 Department of Chemistry, Emory University, Atlanta, Georgia 303222

Received 7 April 2007/ Accepted 25 May 2007

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Pediatrics, 520 Children's Center, 2015 Uppergate Drive, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-1605. Fax: (404) 727-9223. E-mail: rplempe{at}emory.edu

{triangledown} Published ahead of print on 6 June 2007.

Journal of Virology, August 2007, p. 8821-8826, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00754-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Yoon, J.-J., Krumm, S. A., Ndungu, J. M., Hoffman, V., Bankamp, B., Rota, P. A., Sun, A., Snyder, J. P., Plemper, R. K. (2009). Target Analysis of the Experimental Measles Therapeutic AS-136A. Antimicrob. Agents Chemother. 53: 3860-3870 [Abstract] [Full Text]  
  • Lee, J. K., Prussia, A., Paal, T., White, L. K., Snyder, J. P., Plemper, R. K. (2008). Functional Interaction between Paramyxovirus Fusion and Attachment Proteins. J. Biol. Chem. 283: 16561-16572 [Abstract] [Full Text]  


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