Journal
JOURNAL OF VIROLOGY
Volume 80, Issue 17, Pages 8554-8565Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00688-06
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Funding
- MRC [MC_U117512710] Funding Source: UKRI
- Medical Research Council [MC_U117512710] Funding Source: Medline
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Recent studies have revealed the contribution of TRIM 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.
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