All three variable regions of the TRIM5α B30. 2 domain can contribute to the specificity of retrovirus restriction

S Ohkura, MW Yap, T Sheldon, JP Stoye - Journal of virology, 2006 - Am Soc Microbiol
S Ohkura, MW Yap, T Sheldon, JP Stoye
Journal of virology, 2006Am Soc Microbiol
Recent studies have revealed the contribution of TRIM5α to retrovirus restriction in cells from
a variety of primate species. TRIM5α 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 TRIM5α and retrovirus restriction specificity, a series of
chimeric TRIM5α consisting of the human RBCC domain followed by the B30. 2 domain from …
Abstract
Recent studies have revealed the contribution of TRIM5α to retrovirus restriction in cells from a variety of primate species. TRIM5α 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 TRIM5α and retrovirus restriction specificity, a series of chimeric TRIM5α 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 TRIM5αs 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 TRIM5α 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.
American Society for Microbiology