title: Alternative folding nuclei definitions facilitate the evolution of a symmetric protein fold from a smaller peptide motif.
abstract: Protein 3° structure symmetry is a defining feature of nearly one-third of protein folds and is generally thought to result from a combination of gene duplication, fusion, and truncation events. Such events represent major replication errors, involving substantial alteration of protein 3° structure and causing regions of exact repeating 1° structure, both of which are generally considered deleterious to protein folding. Thus, the prevalence of symmetric protein folds is counterintuitive and suggests a specific, yet unexplained, robustness. Using a designed β-trefoil protein, we show that purely symmetric 1° structure enables utilization of alternative definitions of the critical folding nucleus in response to gross structural rearrangement. Thus, major replication errors producing 1° structure symmetry can conserve foldability. The results provide an explanation for the prevalence of symmetric protein folds and highlight a critical role for 1° structure symmetry in protein evolution.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee FL 32306-4300, USA.
authors.forename: Liam M
authors.initials: LM
authors.lastname: Longo
authors.forename: Jihun
authors.initials: J
authors.lastname: Lee
authors.forename: Connie A
authors.initials: CA
authors.lastname: Tenorio
authors.forename: Michael
authors.initials: M
authors.lastname: Blaber
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D016220:Fibroblast Growth Factor 1