Faculty of Chemistry , University of Warsaw , Pasteura 1 , 02-093 , Warsaw , Poland.
Centre of New Technologies , University of Warsaw , Banacha 2c , 02-097 , Warsaw , Poland.
J Phys Chem B. 2018 Dec 13;122(49):11616-11625. doi: 10.1021/acs.jpcb.8b07634. Epub 2018 Oct 12.
The mechanism of folding of deeply knotted proteins into their native structure is still not understood. Current thinking about protein folding is dominated by the Anfinsen dogma, stating that the structure of the folded proteins is uniquely dictated by the amino acid sequence of a given protein and that the folding is driven uniquely by the energy gained from interactions between amino acids that contact each other in the native structure of the protein. The role of ribosomes in protein folding was only seen as permitting the folding to progress from the N-terminal part of nascent protein chains. We propose here that ribosomes can participate actively in the folding of knotted proteins by actively threading nascent chains emerging from the ribosome exit channels through loops formed by a synthesized earlier portion of the same protein. Our simulations of folding of deeply knotted protein Tp0624 positively verify the proposed ribosome-driven active threading mechanism leading to the formation of deeply knotted proteins.
目前对于蛋白质折叠的认识主要受到 Anfinsen 教条的影响，该教条指出折叠蛋白质的结构是由给定蛋白质的氨基酸序列唯一决定的，折叠过程仅由蛋白质天然结构中相互接触的氨基酸之间的相互作用产生的能量驱动。核糖体在蛋白质折叠中的作用仅被视为允许折叠从新生蛋白链的 N 端部分进行。我们在这里提出，核糖体可以通过将从核糖体出口通道中出现的新生链主动穿过由同一蛋白质的早期合成部分形成的环，积极参与打结蛋白的折叠。我们对深度打结蛋白 Tp0624 的折叠模拟实验证实了所提出的核糖体驱动的主动穿线机制，该机制导致了深度打结蛋白的形成。
