The core of swapped-hairpin and double-psi β barrels is formed by duplication of a conserved βαβ element, suggesting a common evolutionary origin. The path connecting the two folds is unclear as the two barrels are not interconvertible by a simple topological modification, such as circular permutation. We have identified a protein family whose sequence properties are intermediate to the two folds. The structure of one of these proteins, Pyrococcus horikoshii PhS018, is also built by duplication of the conserved βαβ element but shows yet a third topology, which we name the RIFT barrel. This topology is widespread in the structure database and spans three folds of the SCOP classification, including the middle domain of EF-Tu and the N domain of F1-ATPase. We propose that swapped-hairpin β barrels arose from an ancestral RIFT barrel by strand invasion and double-psi β barrels by a strand swap. We group the three barrel types into a metafold, the cradle-loop barrels.
Coles M., Hulko M., Djuranovic S., Truffault V., Koretke K., Martin J., Lupas AN. (2006) Common evolutionary origin of swapped-hairpin and double-psi beta barrels.
Structure 14(10):1489-98. (Pubmed
AbrB is a key transition-state regulator of Bacillus subtilis. Based on the conservation of a βαβ structural unit, we proposed a β barrel fold for its DNA binding domain, similar to, but topologically distinct from, double-psi β barrels. However, the NMR structure revealed a novel fold, the "looped-hinge helix." To understand this discrepancy, we undertook a bioinformatics study of AbrB and its homologs; these form a large superfamily, which includes SpoVT, PrlF, MraZ, addiction module antidotes (PemI, MazE), plasmid maintenance proteins (VagC, VapB), and archaeal PhoU homologs. MazE and MraZ form swapped-hairpin β barrels. We therefore reexamined the fold of AbrB by NMR spectroscopy and found that it also forms a swapped-hairpin barrel. The conservation of the core βαβ element supports a common evolutionary origin for swapped-hairpin and double-psi barrels, which we group into a higher-order class, the cradle-loop barrels, based on the peculiar shape of their ligand binding site.
Coles M., Djuranovic S., Söding J., Frickey T., Koretke K., Truffault V., Martin J., Lupas AN. (2005) AbrB-like transcription factors assume a swapped hairpin fold that is evolutionarily related to double-psi β barrels.
Structure 13(6):919-28. (Pubmed