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Journal of Virology, September 2006, p. 8554-8565, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00688-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

All Three Variable Regions of the TRIM5{alpha} B30.2 Domain Can Contribute to the Specificity of Retrovirus Restriction

Sadayuki Ohkura,1 Melvyn W. Yap,1 Tom Sheldon,2 and Jonathan P. Stoye1*

Divisions of Virology,1 Mathematical Biology, National Institute for Medical Research, Medical Research Council, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom2

Received 5 April 2006/ Accepted 12 June 2006

Recent studies have revealed the contribution of TRIM5{alpha} to retrovirus restriction in cells from a variety of primate species. TRIM5{alpha} consists of a tripartite motif (the RBCC domain) followed by a B30.2 domain. The B30.2 domain is thought to be involved in determination of restriction specificity and contains three variable regions. To investigate the relationship between the phylogeny of primate TRIM5{alpha} and retrovirus restriction specificity, a series of chimeric TRIM5{alpha} consisting of the human RBCC domain followed by the B30.2 domain from various primates was constructed. These constructs showed restriction profiles largely consistent with the origin of the B30.2 domain. Restriction specificity was further investigated with a variety of TRIM5{alpha}s containing mixed or mutated B30.2 domains. This study revealed the importance of all three variable regions for determining restriction specificity. Based on the molecular structures of other PRYSPRY domains solved recently, a model for the molecular structure of the B30.2 domain of TRIM5{alpha} was developed. The model revealed that the variable regions of the B30.2 domain are present as loops located on one side of the B30.2 core structure. It is hypothesized that these three loops form a binding surface for virus and that evolutionary changes in any one of the loops can alter restriction specificity.


* Corresponding author. Mailing address: Division of Virology, National Institute for Medical Research, Medical Research Council, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 20 8816 2140. Fax: 44 20 8906 4477. E-mail: jstoye{at}nimr.mrc.ac.uk.


Journal of Virology, September 2006, p. 8554-8565, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00688-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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