Ribosome. Mechanical force releases nascent chain-mediated ribosome arrest in vitro and in vivo.
Ribosome. Mechanical force releases nascent chain-mediated ribosome arrest in vitro and in vivo.
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DOI：
10.1126/science.1261909
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发表时间：
2015-04-24
期刊：
影响因子：
--
通讯作者：
Bustamante C
中科院分区：
文献类型：
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作者：
Goldman DH;Kaiser CM;Milin A;Righini M;Tinoco I Jr;Bustamante C
蛋白质合成速率可以影响基因表达、翻译产物的折叠和活性。新生多肽和核糖体出口通道之间的相互作用代表了调节合成速率的一种模式。SecM蛋白阻止其自身的翻译，并且在转座子上的释放被认为是通过机械力发生的。使用光学镊子，我们证明了secm停滞的核糖体确实可以通过单独的力来拯救，并且释放停滞所需的力可以在体内通过核糖体隧道出口附近的新生链折叠产生。我们制定了一个动力学模型，描述了蛋白质如何通过折叠过程中产生的力来调节自身的合成，调整核糖体活性以获得新生多肽的结构。
Protein synthesis rates can affect gene expression and the folding and activity of the translation product. Interactions between the nascent polypeptide and the ribosome exit tunnel represent one mode of regulating synthesis rates. The SecM protein arrests its own translation, and release of arrest at the translocon has been proposed to occur by mechanical force. Using optical tweezers, we demonstrate that arrest of SecM-stalled ribosomes can indeed be rescued by force alone and that the force needed to release stalling can be generated in vivo by a nascent chain folding near the ribosome tunnel exit. We formulate a kinetic model describing how a protein can regulate its own synthesis by the force generated during folding, tuning ribosome activity to structure acquisition by a nascent polypeptide.