Mechanical Forces Have a Range of Effects on the Rate of Ribosome Catalyzed Peptidyl Transfer Depending on Direction.
Mechanical Forces Have a Range of Effects on the Rate of Ribosome Catalyzed Peptidyl Transfer Depending on Direction.
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DOI：
10.1021/acs.jpcb.1c02263
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发表时间：
2021-07-08
期刊：
影响因子：
--
通讯作者：
O'Brien EP
中科院分区：
文献类型：
--
作者：
Jiang Y;O'Brien EP
作用于位于核糖体P位点的新生链残基上的机械力可以影响密码子翻译速率。迄今为止，大多数观察涉及与核糖体出口隧道的长轴共线对齐的力矢量。人们对在其他方向施加的力如何影响核糖体催化的肽键形成速率知之甚少。在这里，我们利用量子力学/分子力学模拟来估计活化自由能的变化，作为在P-位点的C-末端残基上在各个方向上施加恒定力的结果。与贝尔模型定性一致，我们发现这个力可以加速，减速，或不改变反应速率取决于力的方向。在断裂的P位3′ O-C酯键和形成的肽键之间的平均方向上的力加速了反应。相反方向的力减缓了反应，因为它阻止了这些键的断裂和形成，但令人惊讶的是，它并没有尽可能地做到这一点。在这种情况下，有一种平衡的趋势;这个方向的力使A位点的氨基氮和P位点的tRNA A76 3′氧基团更靠近，这促进了反应中的一个质子穿梭步骤。我们发现最大的力引起的减速发生在偏离该轴37°处。如果在与反应坐标正交的方向上施加力，则反应速度没有显著变化。这些结果表明，有一组更丰富的力对翻译速度的影响的情况下，还有待实验探索，并提高细胞可以使用这些机械化学效应来调节和调节蛋白质合成的可能性。
Mechanical forces acting on the nascent chain residue located at the P-site of the ribosome can influence codon translation rates. Most observations to date involve force vectors aligned collinear with the long axis of the ribosome exit tunnel. What is poorly understood is how force applied in other directions will impact the rate of peptide bond formation catalyzed by the ribosome. Here, we utilize quantum mechanical/molecular mechanics simulations to estimate the changes in the activation free energy as a consequence of applying a constant force in various directions on the C-terminal residue at the P-site. Qualitatively consistent with the Bell model, we find this force can either accelerate, decelerate, or not alter the reaction rate depending on the force direction. A force in the average direction between the P-site 3′ O–C ester bond that breaks and the peptide bond that forms accelerates the reaction. A force in the opposite direction slows down the reaction as it opposes these bonds breaking and forming, but surprisingly it does not do so to the maximum extent possible. In this case, there is a counterbalancing trend; the force in this direction brings the A-site amino nitrogen and the P-site tRNA A76 3′ oxygen groups closer together, which promotes one of the proton shuttling steps of the reaction. We find the maximum force-induced slowdown occurs 37° off this axis. If force is applied in orthogonal directions to the reaction coordinates, there is no significant change in the reaction speed. These results indicate that there is a richer set of scenarios of force effects on translation speed that have yet to be experimentally explored and raise the possibility that cells could use these mechanochemical effects to modulate and regulate protein synthesis.
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影响因子：
16.8
作者：
Ismail, Nurzian;Hedman, Rickard;Schiller, Nina;von Heijne, Gunnar
通讯作者：
von Heijne, Gunnar
DOI：
10.1126/science.1261909
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldman DH;Kaiser CM;Milin A;Righini M;Tinoco I Jr;Bustamante C
通讯作者：
Bustamante C
影响因子：
4.4
作者：
Eyring, H
通讯作者：
Eyring, H
DOI：
10.1073/pnas.141080498
发表时间：
2001-07-03
影响因子：
11.1
作者：
Fisher, ME;Kolomeisky, AB
通讯作者：
Kolomeisky, AB
影响因子：
5.5
作者：
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通讯作者：
Elstner, Marcus