On the energetics of translocon-assisted insertion of charged transmembrane helices into membranes.
On the energetics of translocon-assisted insertion of charged transmembrane helices into membranes.
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关于易位子辅助将带电跨膜螺旋插入膜的能量学。
DOI：
10.1073/pnas.1012207107
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发表时间：
2010
影响因子：
11.1
通讯作者：
Warshel,Arieh
中科院分区：
文献类型：
--
作者：
Rychkova,Anna;Vicatos,Spyridon;Warshel,Arieh
跨膜（TM）螺旋通过易位插入的机制的理解是一个主要的开放挑战。尽管关于膜和溶液之间插入螺旋的分割的实验信息包含了关于这一过程的关键信息，但如何提取这些信息尚不清楚。特别是，目前尚不清楚如何使TM螺旋中心的电离残基的小表观插入能ΔGapp合理化。在这里，我们探索插入能量的本质，询问如果它们的测量值代表平衡条件，这些参数的值应该是什么。这是使用带有高级静电处理的粗粒度模型完成的。估计在邻近螺旋或转座子存在时TM螺旋的电离精氨酸的能量学为观察到的ΔGappof电离残基提供了基本原理。由此得出结论，带电荷残基的TM的表观插入自由能反映的可能不仅仅是将分离的单螺旋从水中移动到膜中的自由能。该方法不仅可用于探索转座子的作用机制，也可用于其他膜蛋白的研究。
The understanding of the mechanism of insertion of transmembrane (TM) helixes through the translocon presents a major open challenge. Although the experimental information about the partition of the inserted helices between the membrane and the solution contains crucial information about this process, it is not clear how to extract this information. In particular, it is not clear how to rationalize the small apparent insertion energy, ΔGapp, of an ionized residue in the center of a TM helix. Here we explore the nature of the insertion energies, asking what should be the value of these parameters if their measurements represent equilibrium conditions. This is done using a coarse-grained model with advanced electrostatic treatment. Estimating the energetics of ionized arginine of a TM helix in the presence of neighboring helixes or the translocon provides a rationale for the observed ΔGappof ionized residues. It is concluded that the apparent insertion free energy of TM with charged residues reflects probably more than just the free energy of moving the isolate single helix from water into the membrane. The present approach should be effective not only in exploring the mechanism of the operation of the translocon but also for studies of other membrane proteins.