Institute of Theoretical and Applied Research, Duy Tan University, Hanoi, Vietnam; Faculty of Pharmacy, Duy Tan University, Da Nang, Vietnam.
Institute of Physics, Vietnam Academy of Science and Technology, Ba Dinh, Hanoi, Vietnam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.
Biophys J. 2021 Nov 2;120(21):4798-4808. doi: 10.1016/j.bpj.2021.09.027. Epub 2021 Sep 21.
After translation, nascent proteins must escape the ribosomal exit tunnel to attain complete folding to their native states. This escape process also frees up the ribosome tunnel for a new translation job. In this study, we investigate the impacts of energetic interactions between the ribosomal exit tunnel and nascent proteins on the protein escape process by molecular dynamics simulations using partially coarse-grained models that incorporate hydrophobic and electrostatic interactions of the ribosome tunnel of Haloarcula marismortui with nascent proteins. We find that, in general, attractive interactions slow down the protein escape process, whereas repulsive interactions speed it up. For the small globular proteins considered, the median escape time correlates with both the number of hydrophobic residues, N, and the net charge, Q, of a nascent protein. A correlation coefficient exceeding 0.96 is found for the relation between the median escape time and a combined quantity of N + 5.9Q, suggesting that it is ∼6 times more efficient to modulate the escape time by changing the total charge than the number of hydrophobic residues. The estimated median escape times are found in the submillisecond-to-millisecond range, indicating that the escape does not delay the ribosome recycling. For various types of the tunnel model, with and without hydrophobic and electrostatic interactions, the escape time distribution always follows a simple diffusion model that describes the escape process as a downhill drift of a Brownian particle, suggesting that nascent proteins escape along barrier-less pathways at the ribosome tunnel.
翻译后，新生蛋白质必须逃离核糖体出口隧道，以达到其天然状态的完全折叠。这个逃离过程还为核糖体隧道腾出空间，以便进行新的翻译工作。在这项研究中，我们通过使用部分粗粒模型的分子动力学模拟来研究核糖体出口隧道和新生蛋白质之间的能量相互作用对蛋白质逃离过程的影响，这些模型纳入了 Haloarcula marismortui 的核糖体隧道与新生蛋白质的疏水性和静电相互作用。我们发现，一般来说，吸引力相互作用会减缓蛋白质的逃离过程，而排斥力相互作用则会加速它。对于所考虑的小球形蛋白质，中位数逃逸时间与疏水性残基数 N 和新生蛋白质的净电荷 Q 都相关。在中位数逃逸时间与 N + 5.9Q 的组合量之间发现了超过 0.96 的相关系数，这表明通过改变总电荷来调节逃逸时间比改变疏水性残基数的效率高约 6 倍。估计的中位数逃逸时间在亚毫秒到毫秒范围内，表明逃离不会延迟核糖体的回收。对于具有和不具有疏水性和静电相互作用的各种类型的隧道模型，逃逸时间分布始终遵循简单的扩散模型，该模型将逃离过程描述为布朗粒子的下坡漂移，这表明新生蛋白质沿着核糖体隧道的无阻碍途径逃离。
