title: De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints.
abstract: Molecular evolution has focused on the divergence of molecular functions, yet we know little about how structurally distinct protein folds emerge de novo. We characterized the evolutionary trajectories and selection forces underlying emergence of β-propeller proteins, a globular and symmetric fold group with diverse functions. The identification of short propeller-like motifs (<50 amino acids) in natural genomes indicated that they expanded via tandem duplications to form extant propellers. We phylogenetically reconstructed 47-residue ancestral motifs that form five-bladed lectin propellers via oligomeric assembly. We demonstrate a functional trajectory of tandem duplications of these motifs leading to monomeric lectins. Foldability, i.e., higher efficiency of folding, was the main parameter leading to improved functionality along the entire evolutionary trajectory. However, folding constraints changed along the trajectory: initially, conflicts between monomer folding and oligomer assembly dominated, whereas subsequently, upon tandem duplication, tradeoffs between monomer stability and foldability took precedence.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Smock
authors.affiliation: Metabolic Pathways and Enzyme Evolution Laboratory, Migal Galilee Research Institute, Kiryat Shmona 11016, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Yadid
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Dym
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Clarke
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: dan.tawfik@weizmann.ac.il.
authors.forename: Dan S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D020440:Gene Duplication; D006737:Horseshoe Crabs; D037102:Lectins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017510:Protein Folding; D012615:Sea Anemones; D016415:Sequence Alignment
chemical_list: D060829:Arthropod Proteins; D037102:Lectins