TY - JOUR
T1 - Foldability of a Natural De Novo Evolved Protein
AU - Bungard, Dixie
AU - Copple, Jacob S.
AU - Yan, Jing
AU - Chhun, Jimmy J.
AU - Kumirov, Vlad K.
AU - Foy, Scott G.
AU - Masel, Joanna
AU - Wysocki, Vicki H.
AU - Cordes, Matthew H.J.
N1 - Funding Information:
This work was supported by NIH grant GM104040 (R01 to M.H.J.C. and J.M.), GM113658 (to V.H.W.), and John Templeton Foundation grant 39667 (to J.M.). Mass spectrometry data for limited proteolysis experiments were acquired by the Arizona Proteomics Consortium supported by NIEHS grant ES06694 to SWEHSC, NIH/NCI grant CA023074 to the UA Cancer Center, and by the Bio5 Institute of the University of Arizona. The Thermo Fisher LTQ Orbitrap Velos mass spectrometer was provided by grant 1S10 RR028868-01 from NIH/NCRR.
Funding Information:
This work was supported by NIH grant GM104040 (R01 to M.H.J.C. and J.M.), GM113658 (to V.H.W.), and John Templeton Foundation grant 39667 (to J.M.). Mass spectrometry data for limited proteolysis experiments were acquired by the Arizona Proteomics Consortium supported by NIEHS grant ES06694 to SWEHSC, NIH/ NCI grant CA023074 to the UA Cancer Center, and by the Bio5 Institute of the University of Arizona . The Thermo Fisher LTQ Orbitrap Velos mass spectrometer was provided by grant 1S10 RR028868-01 from NIH/ NCRR .
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/11/7
Y1 - 2017/11/7
N2 - 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.
AB - 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.
KW - amyloid oligomer
KW - conformational specificity
KW - de novo protein
KW - de novo protein-coding gene
KW - molten globule
KW - partially folded protein
KW - protein folding
KW - structural evolution
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U2 - 10.1016/j.str.2017.09.006
DO - 10.1016/j.str.2017.09.006
M3 - Article
C2 - 29033289
AN - SCOPUS:85031299166
SN - 0969-2126
VL - 25
SP - 1687-1696.e4
JO - Structure
JF - Structure
IS - 11
ER -