title: All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction.
abstract: Recent studies have revealed the contribution of TRIM5alpha to retrovirus restriction in cells from a variety of primate species. TRIM5alpha 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 TRIM5alpha and retrovirus restriction specificity, a series of chimeric TRIM5alpha 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 TRIM5alphas 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 TRIM5alpha 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.
authors.affiliation: Division of Virology, National Institute for Medical Research, Medical Research Council, London, UK.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Ohkura
authors.forename: Melvyn W
authors.initials: MW
authors.lastname: Yap
authors.forename: Tom
authors.initials: T
authors.lastname: Sheldon
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stoye
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D018420:Ape Diseases / Q000821:virology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D015497:HIV-1 / Q000472:pathogenicity; D000882:Haplorhini / Q000821:virology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D051379:Mice; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000821:virology*; D010802:Phylogeny; D012190:Retroviridae / Q000472:pathogenicity*; D012192:Retroviridae Infections / Q000662:veterinary* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases