Department of Physical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
Department of Physical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
Biophys J. 2022 Dec 6;121(23):4443-4451. doi: 10.1016/j.bpj.2022.11.004. Epub 2022 Nov 5.
Proteosynthesis on ribosomes is regulated at many levels. Conformational changes of the ribosome, possibly induced by external factors, may transfer over large distances and contribute to the regulation. The molecular principles of this long-distance allostery within the ribosome remain poorly understood. Here, we use structural analysis and atomistic molecular dynamics simulations to investigate peptide deformylase (PDF), an enzyme that binds to the ribosome surface near the ribosomal protein uL22 during translation and chemically modifies the emerging nascent peptide. Our simulations of the entire ribosome-PDF complex reveal that the PDF undergoes a swaying motion on the ribosome surface at the submicrosecond timescale. We show that the PDF affects the conformational dynamics of parts of the ribosome over distances of more than 5 nm. Using a supervised-learning algorithm, we demonstrate that the exit tunnel is influenced by the presence or absence of PDF. Our findings suggest a possible effect of the PDF on the nascent peptide translocation through the ribosome exit tunnel.
核糖体上的蛋白合成受到多个层面的调控。核糖体的构象变化，可能由外部因素诱导，可远距离传递，并有助于调控。核糖体内部这种远距离变构作用的分子原理仍知之甚少。在这里，我们使用结构分析和原子分子动力学模拟来研究肽脱甲酰基酶（PDF），一种在翻译过程中结合在核糖体表面靠近核糖体蛋白 uL22 上的酶，并对新生肽进行化学修饰。我们对整个核糖体-PDF 复合物的模拟显示，PDF 在亚微秒时间尺度上在核糖体表面上进行摆动运动。我们表明，PDF 影响核糖体上超过 5nm 的部分构象动力学。我们使用监督学习算法，证明了出口隧道受到 PDF 存在与否的影响。我们的发现表明 PDF 可能对新生肽通过核糖体出口隧道的易位产生影响。
