Foldability of a Natural De Novo Evolved Protein

Dixie Bungard, Jacob S. Copple, Jing Yan, Jimmy J. Chhun, Vlad K. Kumirov, Scott G. Foy, Joanna Masel, Vicki H. Wysocki, Matthew Hj Cordes

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo. Recent studies have shown that new protein-coding genes can arise ". de novo" from noncoding DNA. The properties of the brand new proteins encoded by these genes remain poorly understood. Here, Bungard et al. show that a very young de novo protein from yeast folds to a partially ordered three-dimensional structure.

Original languageEnglish (US)
JournalStructure
DOIs
Publication statusAccepted/In press - 2017

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Keywords

  • Amyloid oligomer
  • Conformational specificity
  • de novo protein
  • de novo protein-coding gene
  • Molten globule
  • Partially folded protein
  • Protein folding
  • Structural evolution

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Bungard, D., Copple, J. S., Yan, J., Chhun, J. J., Kumirov, V. K., Foy, S. G., ... Cordes, M. H. (Accepted/In press). Foldability of a Natural De Novo Evolved Protein. Structure. https://doi.org/10.1016/j.str.2017.09.006