Department of Chemistry & Biochemistry, Knoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208.
Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2216308120. doi: 10.1073/pnas.2216308120. Epub 2023 May 8.
Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of . However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in further demonstrate that these G4s primarily improve protein folding quality in as opposed to preventing protein aggregation. The ability of a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins.
维持蛋白质组的健康是细胞的一项关键任务。最近，我们发现 G-四链体 (G4) 核酸在体外特别有效地防止蛋白质聚集，并至少可以间接地改善蛋白质的折叠环境。然而，G4 在蛋白质折叠中的作用尚未得到探索。在这里，通过体外蛋白质折叠实验，我们发现 G4 可以通过将动力学捕获的中间体恢复到天然和近天然折叠状态来加速蛋白质折叠。在 中的时程折叠实验进一步表明，这些 G4 主要改善了 中的蛋白质折叠质量，而不是防止蛋白质聚集。短核酸恢复蛋白质折叠的能力为核酸和 ATP 非依赖性伴侣在决定蛋白质最终折叠命运方面发挥重要作用提供了可能性。
