title: Evolutionary relationship of two ancient protein superfolds.
abstract: Proteins are the molecular machines of the cell that fold into specific three-dimensional structures to fulfill their functions. To improve our understanding of how the structure and function of proteins arises, it is crucial to understand how evolution has generated the structural diversity we observe today. Classically, proteins that adopt different folds are considered to be nonhomologous. However, using state-of-the-art tools for homology detection, we found evidence of homology between proteins of two ancient and highly populated protein folds, the (βα)8-barrel and the flavodoxin-like fold. We detected a family of sequences that show intermediate features between both folds and determined what is to our knowledge the first representative crystal structure of one of its members, giving new insights into the evolutionary link of two of the earliest folds. Our findings contribute to an emergent vision where protein superfolds share common ancestry and encourage further approaches to complete the mapping of structure space onto sequence space.
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: José Arcadio
authors.initials: JA
authors.lastname: Farías-Rico
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Birte
authors.identifier: 0000000282509462
authors.initials: B
authors.lastname: Höcker
mesh_terms: D000595:Amino Acid Sequence; D005075:Biological Evolution; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005418:Flavodoxin / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D017385:Sequence Homology
chemical_list: D005418:Flavodoxin; D011506:Proteins