Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea; Vaccine Innovation Technology Alliance (VITAL)-Korea, Yonsei University, Seoul 03722, Republic of Korea.
Curr Opin Struct Biol. 2021 Feb;66:104-111. doi: 10.1016/j.sbi.2020.10.014. Epub 2020 Nov 22.
Protein folding in vivo has been largely understood in the context of molecular chaperones preventing aggregation of nascent polypeptides in the crowded cellular environment. Nascent chains utilize the crowded environment in favor of productive folding by direct physical connection with cellular macromolecules. The intermolecular repulsive forces by large excluded volume and surface charges of interacting cellular macromolecules, exerting 'social distancing' measure among folding intermediates, could play an important role in stabilizing their physically connected polypeptides against aggregation regardless of the physical connection types. The generic intrinsic chaperone activity of cellular macromolecules likely provides a robust cellular environment for the productive protein folding and solubility maintenance at the whole proteome level.
在细胞拥挤的环境中，新生多肽易发生聚集，分子伴侣可防止其聚集，在此背景下，人们对体内蛋白质折叠已有了深入的了解。新生链通过与细胞大分子的直接物理连接，利用拥挤的环境促进其有效折叠。由于大的排阻体积和相互作用的细胞大分子的表面电荷产生的分子间斥力，在折叠中间体之间施加“社交距离”措施，即使不考虑物理连接类型，也可能在稳定其物理连接的多肽防止聚集方面发挥重要作用。细胞大分子的通用内在伴侣活性可能为整个蛋白质组水平的有效蛋白质折叠和可溶性维持提供了稳健的细胞环境。
