De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints
Smock, Robert G
Tawfik, Dan SS
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Smock, R. G., Yadid, I., Dym, O., Clarke, J., & Tawfik, D. S. (2016). De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints. Cell, 164 476-486. https://doi.org/10.1016/j.cell.2015.12.024
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.
protein birth, molecular evolution, gene duplication, fusion and divergence, propeller, lectin, multidomain, repeat protein, protein folding, stability, domain swap, internal friction
We thank Michael Gurevitz (Tel Aviv University), John Finnerty (Boston University) and Adam Reitzel (Woodshole Oceanographic Institute) for providing N. vectensis cDNA, and Joseph Rogers (University of Cambridge) for discussion and assistance. We thank Liam Longo, Ron Milo and Balaji Santhanam for insightful comments on this manuscript. This work was supported by the Israel Science Foundation grant 980/14 (DST), the Weizmann - UK Joint Research Program (DST and JC), the Weizmann Koshland and Dean of Faculty fellowships (RGS) and an EMBO short-term fellowship (RGS). JC is a Wellcome Trust Fellow (WT 095195).
Wellcome Trust (095195/Z/10/Z)
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External DOI: https://doi.org/10.1016/j.cell.2015.12.024
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253187