Institute for Advanced Studies in Theoretical Chemistry, Technion, Israel Institute of Technology, Technion City, Haifa 32000, Israel.
FASEB J. 2012 Jun;26(6):2277-82. doi: 10.1096/fj.11-197657. Epub 2012 Mar 2.
The ribosome is a molecular machine whose manner of controlling the progression of the nascent chain through the ribosomal exit tunnel is currently unknown. A novel model for the mechanism driving the nascent chain motion is hereby presented, in which the ∼180° rotatory motion performed by each C-terminal amino acid of the nascent chain during its translocation from the A site to the P site, is suggested to twist the newly formed peptide bond into cis conformation. By catalyzing the cis to trans isomerization, the ribosome is proposed to release the potential energy stored within the cis conformer and to utilize it to push the chain down the tunnel, thus operating as a molecular motor. This hypothetical isomerization mechanism is supported by its ability to provide an explanation for the peculiar conduct observed in translational events of nascent chains with C-terminal prolines: the slow peptide bond formation with puromycin, translation arrest, and tmRNA tagging.
核糖体是一种分子机器，其控制新生肽链通过核糖体出口隧道的方式目前尚不清楚。本文提出了一种新生肽链运动机制的新模型，其中新生肽链从 A 位到 P 位转移过程中每个 C 末端氨基酸进行的约 180°旋转运动，被认为是将新形成的肽键扭转成顺式构象。通过催化顺式到反式异构化，核糖体被提出释放顺式构象中储存的势能，并利用它将链向下推过隧道，从而充当分子马达。这种假设的异构化机制能够解释带有 C 末端脯氨酸的新生肽链翻译事件中观察到的特殊行为：与嘌呤霉素的肽键形成缓慢、翻译暂停和 tmRNA 标记。
