title: AbrB-like transcription factors assume a swapped hairpin fold that is evolutionarily related to double-psi beta barrels.
abstract: AbrB is a key transition-state regulator of Bacillus subtilis. Based on the conservation of a betaalphabeta structural unit, we proposed a beta barrel fold for its DNA binding domain, similar to, but topologically distinct from, double-psi beta 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 beta 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 betaalphabeta 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.
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany.
authors.forename: Murray
authors.initials: M
authors.lastname: Coles
authors.forename: Sergej
authors.initials: S
authors.lastname: Djuranovic
authors.forename: Johannes
authors.initials: J
authors.lastname: Söding
authors.forename: Tancred
authors.initials: T
authors.lastname: Frickey
authors.forename: Kristin
authors.initials: K
authors.lastname: Koretke
authors.forename: Vincent
authors.initials: V
authors.lastname: Truffault
authors.forename: Jörg
authors.initials: J
authors.lastname: Martin
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000254:growth & development / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016000:Cluster Analysis; D017124:Conserved Sequence; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors