Protein salvage and repurposing in evolution: Phospholipase D toxins are stabilized by a remodeled scrap of a membrane association domain.

The glycerophosphodiester phosphodiesterase (GDPD)-like SMaseD/PLD domain family, which includes phospholipase D (PLD) toxins in recluse spiders and actinobacteria, evolved anciently in bacteria from the GDPD. The PLD enzymes retained the core (β/α) barrel fold of GDPD, while gaining a signature C-terminal expansion motif and losing a small insertion domain. Using sequence alignments and phylogenetic analysis, we infer that the C-terminal motif derives from a segment of an ancient bacterial PLAT domain.