Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0088, USA.
Department of Chemistry and Biochemistry, Ohio State University Columbus, Columbus, OH 43210-1173, USA.
Structure. 2017 Nov 7;25(11):1687-1696.e4. doi: 10.1016/j.str.2017.09.006. Epub 2017 Oct 12.
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.
从头起源的蛋白质编码基因从非编码 DNA 进化而来，这一现象正在成为生物学中分子创新的一个来源。然而，对随机序列文库的研究表明，新产生的蛋白质不会折叠成具有特定结构的紧凑的、典型的天然球状蛋白质。在这里，我们展示了 Bsc4，这是一种功能性的、天然的从头起源的蛋白质，由酵母 S. cerevisiae 中非编码 DNA 中最近进化而来的基因编码。Bsc4 折叠成具有部分特定三维结构的形式。Bsc4 形成可溶性的、紧凑的寡聚物，具有高β片层含量和疏水核心，并经历协同的、可逆的变性。然而，Bsc4 缺乏特定的四级状态，而是存在于寡聚体大小的连续分布中，并结合染料，表明其为淀粉样寡聚物或熔融球蛋白。这种类似天然和非天然性质的组合表明，它可能作为新折叠蛋白质从头起源的功能性中间产物的原始折叠。
