pH (low) insertion peptide (pHLIP) inserts across a lipid bilayer as a helix and exits by a different path
pH (low) insertion peptide (pHLIP) inserts across a lipid bilayer as a helix and exits by a different path
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DOI：
10.1073/pnas.0914330107
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发表时间：
2010-03-02
影响因子：
11.1
通讯作者：
Reshetnyak, Yana K.
中科院分区：
文献类型：
--
作者：
Andreev, Oleg A.;Karabadzhak, Alexander G.;Reshetnyak, Yana K.
当一个肽穿过膜插入或离开膜时，会发生什么样的分子事件？使用pH触发的插入的pH低插入肽，使动力学分析，我们表明，插入发生在几个步骤中，快速（0.1秒）界面螺旋形成，然后由一个慢得多（100秒）的插入途径，得到一个跨膜螺旋。展开和肽从双层核心退出的反向过程，可以通过pH从酸性到碱性的快速上升来诱导，比折叠/插入快大约400倍，并且通过不同的中间状态。在出口途径中，当多肽仍在膜内时，螺旋-卷曲转变开始。当大约30%的螺旋展开时，肽开始退出，并且当它在膜内展开时继续快速退出。这些见解可能会指导膜蛋白折叠/展开的理解和医学上有用的肽成像和药物输送的设计。
What are the molecular events that occur when a peptide inserts across a membrane or exits from it? Using the pH-triggered insertion of the pH low insertion peptide to enable kinetic analysis, we show that insertion occurs in several steps, with rapid (0.1 sec) interfacial helix formation, followed by a much slower (100 sec) insertion pathway to give a transmembrane helix. The reverse process of unfolding and peptide exit from the bilayer core, which can be induced by a rapid rise of the pH from acidic to basic, proceeds approximately 400 times faster than folding/insertion and through different intermediate states. In the exit pathway, the helix-coil transition is initiated while the polypeptide is still inside the membrane. The peptide starts to exit when about 30% of the helix is unfolded, and continues a rapid exit as it unfolds inside the membrane. These insights may guide understanding of membrane protein folding/unfolding and the design of medically useful peptides for imaging and drug delivery.