Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Department of Pharmacy, Ewha Womans University, Seoul, 03760, Republic of Korea.
Sci Rep. 2019 Feb 25;9(1):2735. doi: 10.1038/s41598-019-39158-6.
Molecular chaperones play an important role in cellular protein-folding assistance and aggregation inhibition. As a different but complementary model, we previously proposed that, in general, soluble cellular macromolecules with large excluded volume and surface charges exhibit intrinsic chaperone activity to prevent aggregation of their connected polypeptides irrespective of the connection type, thereby contributing to efficient protein folding. As a proof of concept, we here demonstrated that a model recombinant protein with a specific sequence-binding domain robustly exerted chaperone activity toward various proteins harbouring a short recognition tag of 7 residues in Escherichia coli. The chaperone activity of this protein was comparable to that of representative E. coli chaperones in vivo. Furthermore, in vitro refolding experiments confirmed the in vivo results. Our findings reveal that a soluble protein exhibits the intrinsic chaperone activity to prevent off-pathway aggregation of its interacting proteins, leading to more productive folding while allowing them to fold according to their intrinsic folding pathways. This study gives new insights into the plausible chaperoning role of soluble cellular macromolecules in terms of aggregation inhibition and indirect folding assistance.
分子伴侣在细胞蛋白折叠辅助和聚集抑制中发挥着重要作用。作为一个不同但互补的模型，我们之前提出，一般来说，具有大排斥体积和表面电荷的可溶性细胞大分子表现出内在的伴侣活性，以防止与其连接的多肽聚集，而不管连接类型如何，从而有助于有效的蛋白质折叠。作为一个概念验证，我们在这里证明了一种具有特定序列结合结构域的模型重组蛋白在大肠杆菌中对各种含有 7 个残基短识别标签的蛋白质表现出强烈的伴侣活性。该蛋白的伴侣活性与代表性大肠杆菌伴侣蛋白在体内相当。此外，体外重折叠实验证实了体内结果。我们的发现表明，可溶性蛋白具有内在的伴侣活性，可防止其相互作用蛋白的非通路聚集，从而在允许它们根据自身内在折叠途径折叠的同时，提高折叠效率。这项研究为可溶性细胞大分子在聚集抑制和间接折叠辅助方面可能的伴侣作用提供了新的见解。
