On the evolution of alternate core packing in eightfold beta/alpha-barrels

Two sequence-related subfamilies of flavin-binding beta/alpha-barrels have been identified (the type I and type II proteins) that differ in the nature of residue packing in the core of the barrel domain. Similar observed differences in the packing of internal amino acid side chains in beta/alpha-barrels have previously been used to argue that these domains have evolved convergently toward a stable structural framework. Using structural alignments of flavin-binding barrel proteins, we demonstrate that simple genetic alterations may be responsible for switching the nature of side-chain packing observed in beta/alpha-barrels. The implication is that the 2 structural classes of beta/alpha-barrel cores can arise divergently from an ancestral barrel framework and that convergent evolution to a stable fold need not be invoked to account for the emergence of 2 classes of beta/alpha-barrel core.