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首页> 外文期刊>Journal of Molecular Biology >Repetitive pulling catalyzes co-translocational unfolding of barnase during import through a mitochondrial pore
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Repetitive pulling catalyzes co-translocational unfolding of barnase during import through a mitochondrial pore

机译：在通过线粒体孔导入过程中，反复拉动可催化barnase的共移位

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摘要

We present a computational study of barnase unfolding during import into mitochondria through a model translocon. In contrast to thermal (or chemical) unfolding, the major intermediates of co-translocational unfolding are mainly mediated by non-native interactions accompanying the protein configurations induced by pulling forces. These energy contributions, combined with backbone topological constraints imposed by the model pore, result in milestones along the unfolding pathways which are significantly different not only from those experienced during thermal (or chemical) denaturation, but also from those observed in single-molecule pulling by both ends without pore constraints. Two on-pathway major translocation intermediates trapped in long-lived states by significantly high unfolding barriers are identified. A fraction of these pathways can, however, skip such local kinetic traps and result in extremely fast translocations, leading to a dramatic kinetic partitioning spanning approximately four orders of magnitude. The fraction of fast translocation events is shown to increase upon switching the pull off and on, when compared to pulling at constant force. This suggests a "catalytic" mechanism by which the mitochondrial import machinery regulates this partitioning by repetitively pulling in cycles. A number of mutation sites that alter the kinetic "flow" of the unfolding trajectories are suggested and tested. (c) 2005 Elsevier Ltd. All rights reserved.
机译：我们提出通过模型translocon进入线粒体期间barnase展开的计算研究。与热（或化学）展开相反，共易位展开的主要中间体主要由伴随拉力诱导的蛋白质构型的非天然相互作用介导。这些能量贡献与模型孔隙施加的主干拓扑约束相结合，导致沿展开路径的里程碑不仅与热（或化学）变性过程中经历的里程碑显着不同，而且还与单分子拉制过程中观察到的显着不同。两端无孔约束。鉴定出两个生命途中的主要易位中间体，这些中间体被显着高的展开障碍困在长寿状态。但是，这些途径中的一小部分可以跳过此类局部动力学陷阱，并导致极快的移位，从而导致跨越约四个数量级的剧烈动力学分区。与以恒定力拉动相比，快速拉动事件的分数显示出在拉开和拉开时增加。这表明线粒体输入机制通过反复拉动循环来调节这种分配的“催化”机制。建议并测试了许多改变展开轨迹的动力学“流动”的突变位点。 （c）2005 Elsevier Ltd.保留所有权利。

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