Saturday, September 3, 2011

The remarkable story of the mutagenic AID/APOBECs and other deaminases

The nucleotide and nucleic acid deaminases such as CDD1, ADAR, TadA/Tad2, AID, APOBEC and DYW catalyze  deamination of nucleotide or nucleic acid bases in a wide range of contexts. Of these, some of the most remarkable ones are the nucleic acid deaminases such as AID/APOBEC, ADAR and DYW that modify bases in nucleic acids in a range of contexts such as  organellar RNA editing, hypermutation of viruses and the  generation of  hypervariability in proteins involved in adaptive immunity. One characteristic of these that was most mystifying was the limited phyletic distribution of some families and their rapid evolution.In a comprehensive sequence-structure analysis of the deaminase superfamily, we now uncover several aspects that were previously unclear, including the overall history of the fold with respect to protein superfamilies such as the JAB peptidases. We report several new families of which the most remarkable are deaminases that serve as toxins in bacterial polymorphic toxin systems. Several new and interesting candidates in eukaryotes are also identified. Watch this space for key highlights. For now you can read the paper. Click here to access the paper. There is an extensive supplement available here.