Abstract
SummaryMolecular 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.
Highlights
The birth of new proteins is essential to the diversity of life, in cellular signaling and immunity (Chen et al, 2013)
Symmetry is dominant in all b proteins, and distinctly in b propellers (Balaji, 2015). b Propellers are associated with diverse functions in immunorecognition, viral infection, signal transduction, and vesicle formation
We subsequently examined how these motifs further evolve by tandem duplications, diversification, and topological permutation to yield highly functional monomeric lectins (Figure 2)
Summary
The birth of new proteins is essential to the diversity of life, in cellular signaling and immunity (Chen et al, 2013). Topological permutations are a commonly observed genetic rearrangement, involving duplication, fusion, and truncation (new start and stop codons) that effectively transpose residues between protein termini (‘‘circular permutation’’; Figures 1B and 1C). These permutations shift the boundaries between sequence motifs and structural domains (Longo et al, 2013; Peisajovich et al, 2006), as seen in the ‘‘Velcro closure’’ topology of propellers (Figures 1A–1C). For these mechanisms to be evolutionary feasible, the genetic processes generating new DNA sequences must be coupled with protein intermediates that are foldable, stable, and biochemically active
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