ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach
ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach
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DOI：
10.1016/j.steroids.2012.02.022
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发表时间：
2012-08-01
期刊：
影响因子：
2.7
通讯作者：
Jacquot, Yves
中科院分区：
文献类型：
--
作者：
Byrne, Cillian;Khemtemourian, Lucie;Jacquot, Yves
最近，我们鉴定了一种肽（ER α 17p，P(295)LMIKRSKKNSLALSLT(311)），它对应于雌激素受体 a（ER α，铰链区）的 295-311 序列，并且在乳腺癌细胞中发挥一系列药理作用。值得注意的是，这些效应可能是 ER α 17p 与质膜相互作用的结果。在此，我们表明，ER α 17p 在与阴离子磷脂接触时采用 β 片层二级结构，并被脂质双层吞没。虽然 ER α 17p 增加了膜模拟物的流动性，但它在活细胞中的内化作用较弱。鉴于上述情况，人们可能会想到 ER α 的 295-311 区域的一个重要作用：相应的肽可以分泌/递送到细胞外介质，以在细胞内和膜水平上与邻近细胞相互作用。最后，ER α 的 295-311 区域靠近半胱氨酸 447，ERa 的棕榈酰化位点提出了其参与蛋白质与膜的相互作用/稳定化的问题。 (c) 2012 Elsevier Inc. 保留所有权利。
Recently, we identified a peptide (ER alpha 17p, P(295)LMIKRSKKNSLALSLT(311)) that corresponds to the 295-311 sequence of the estrogen receptor a (ER alpha, hinge region) and which exerts a panel of pharmacological effects in breast cancer cells. Remarkably, these effects can result from the interaction of ER alpha 17p with the plasma membrane. Herein, we show that ER alpha 17p adopts a beta-sheet secondary structure when in contact with anionic phospholipids and that it is engulfed within the lipid bilayer. While ER alpha 17p increases the fluidity of membrane mimics, it weakly internalizes in living cells. In light of the above, one may evoke one important role of the 295-311 region of the ER alpha: the corresponding peptide could be secreted/delivered to the extracellular medium to interact with neighboring cells, both intracellularly and at the membrane level. Finally, the 295-311 region of ER alpha being in proximity to the cystein-447, the palmitoylation site of the ERa raises the question of its involvement in the interaction/stabilization of the protein with the membrane. (c) 2012 Elsevier Inc. All rights reserved.