Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion.

Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion.
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DOI:
10.1038/ncomms5863
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发表时间:
2014-09-10
影响因子:
16.6
通讯作者:
White, Stephen H.
White, Stephen H.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ulmschneider, Martin B.;Ulmschneider, Jakob P.;Schiller, Nina;Wallace, B. A.;von Heijne, Gunnar;White, Stephen H.

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跨膜(TM)α-螺旋在水相和脂质双层之间的有利转移自由能是膜蛋白稳定性的基础。然而,Sec 61/SecY转运子复合物在体内的能量学和膜蛋白组装过程之间的联系尚不清楚。在这里,我们直接确定分区自由能的一个家庭的设计肽使用三个独立的方法:实验微粒体Sec 61易位测定,生物物理(光谱)表征肽插入到水化平面脂质双层阵列,和一个公正的原子细节平衡折叠分区分子动力学模拟。值得注意的是,所测得的插入自由能是定量相似的所有三种方法。分子动力学模拟表明,TM螺旋插入涉及与膜界面的平衡,这表明界面可能在translocon引导插入中发挥作用。
The favorable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.
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影响因子: 3.3
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