We have a new paper out today in Scientific Reports “Prototype foamy virus intasome aggregation is mediated by outer protein domains and prevented by protocatechuic acid“.
PFV intasomes are a tetramer of integrase bound to viral DNA ends with two catalytically active “inner” and structural “outer” integrase subunits. Directing truncation mutants to the outer integrases revealed that the carboxyl terminal domains (CTDs) play a substantial role in the aggregation of intasomes. This phenomenon shortens the lifetime of an integration reaction in vitro. Aggregation is prevented by including higher than physiological salt concentration or a small molecule protocatechuic acid (PCA). PCA is commonly used in oxygen scavenging systems to prevent fluorophore photobleaching. Addition of PCA to PFV integration reactions in vitro prevents aggregation at physiologically relevant ionic conditions.