AI 中文总结
研究核糖体通道内在方向性，通过有偏分子动力学模拟及聚丙氨酸十肽模型，比较正向和反向肽转运，发现通道结构利于自然方向转运，反向转运的蛋白质可能需专门机制克服内在偏向。
AI 中文摘要
在成熟之前，所有已知蛋白质都以延伸或部分折叠的新生多肽形式通过核糖体出口通道转运。这种转运沿自然方向发生，即从深埋在大核糖体亚基中的肽基转移酶中心通过通道到核糖体表面。然而，一些蛋白质从外部进入核糖体通道并反向转运。在这项工作中，我们探讨一个简单问题：核糖体通道在多大程度上具有内在方向性。为比较正向和反向肽转运，我们进行有偏分子动力学模拟，并使用聚丙氨酸十肽模型评估来自四种不同生物体的通道方向性。我们的模拟表明，通道结构本质上有利于从肽基转移酶中心到核糖体表面的自然方向转运。因此，反向占据通道的蛋白质可能需要专门的结构机制来克服这种内在偏向。
英文摘要
Before they mature, all known proteins translocate through the ribosomal exit tunnel in a form of extended or partially folded nascent polypeptide. This translocation occurs in the natural direction from the peptidyl transferase centre buried deep in the large ribosomal subunit through a tunnel to the ribosomal surface. Some proteins, however, enter the ribosomal tunnel from outside and translocate in the reverse direction. In this work, we address a simple question: to what extent is the ribosomal tunnel intrinsically directional. To compare the forward and reverse peptide translocations, we performed biased molecular dynamics simulations and assessed the directionality of tunnels from four different organisms using a model poly-alanine decapeptide. Our simulations reveal that the tunnel architecture intrinsically favours the natural direction translocation from peptidyl transferase centre to the ribosomal surface. Consequently, proteins that occupy the tunnel in the reverse direction likely require dedicated structural machinery to overcome this intrinsic bias.
Comments17 pages, 5 figures
