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Journal of Virology, August 2006, p. 8225-8235, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00395-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Characterization of an Amino-Terminal Dimerization Domain from Retroviral Restriction Factor Fv1

Kate N. Bishop,1,{dagger} Gulnahar B. Mortuza,2 Steven Howell,2 Melvyn W. Yap,1 Jonathan P. Stoye,1 and Ian A. Taylor2*

Divisions of Virology,1 Protein Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom2

Received 24 February 2006/ Accepted 23 May 2006

The Fv1 protein is an endogenous factor in mice that confers resistance to infection by certain classes of murine leukemia virus, a phenomenon referred to as restriction. The mechanism of restriction is not understood, and the low endogenous level of Fv1 in cells has prevented any biochemical or biophysical analysis of the protein. We have now purified recombinant Fv1n protein from a baculovirus system and demonstrate that Fv1 exists in a multimeric form. Furthermore, we have mapped the position of two domains within the protein using limited proteolysis. Biophysical characterization of the N-terminal domain reveals that it comprises a highly helical and extended dimeric structure. Based on these biochemical and biophysical data, we propose a model for the arrangement of domains in Fv1 and suggest that dimerization of the N-terminal domain is necessary for Fv1 function to allow the protein to interact with multiple capsid protomers in retroviral cores.


* Corresponding author. Mailing address: Division of Protein Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 20 8816 2552. Fax: 44 20 8816 2580. E-mail: itaylor{at}nimr.mrc.ac.uk.

{dagger} Present address: Department of Infectious Diseases, King's College London, London SE1 9RT, United Kingdom.


Journal of Virology, August 2006, p. 8225-8235, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00395-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.