Pleiotropic effects of membrane cholesterol upon translocation of protein across the endoplasmic reticulum membranes
Pleiotropic effects of membrane cholesterol upon translocation of protein across the endoplasmic reticulum membranes
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膜胆固醇对蛋白质跨内质网膜易位的多效性作用
DOI：
10.1021/bi2018915
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kida Y ; Sakaguchi M.
中科院分区：
文献类型：
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作者：
Yamamoto H;Fuiita H;Kida Y ; Sakaguchi M.
各种蛋白质通过易位子通道易位并插入内质网膜。信号序列的疏水片段启动易位，而易位多肽上的疏水片段则中断易位以插入膜中。正电荷抑制易位以调节信号序列的方向。在这里，我们研究了膜胆固醇对无细胞系统中新生链易位行为的影响。我们发现三种不同的易位过程对膜胆固醇敏感。胆固醇通过信号序列抑制易位的启动，并且抑制的程度取决于信号序列。即使起始未被抑制，胆固醇也会阻碍易位多肽链带正电残基的运动。令人惊讶的是，胆固醇通过易位子增强了疏水序列的易位。基于这些发现，我们提出膜胆固醇极大地影响疏水片段在膜中的分配并阻碍正电荷的移动。
Various proteins are translocated through and inserted into the endoplasmic reticulum membrane via translocon channels. The hydrophobic segments of signal sequences initiate translocation, and those on translocating polypeptides interrupt translocation to be inserted into the membrane. Positive charges suppress translocation to regulate the orientation of the signal sequences. Here, we investigated the effect of membrane cholesterol on the translocational behavior of nascent chains in a cell-free system. We found that the three distinct translocation processes were sensitive to membrane cholesterol. Cholesterol inhibited the initiation of translocation by the signal sequence, and the extent of inhibition depended on the signal sequence. Even when initiation was not inhibited, cholesterol impeded the movement of the positively charged residues of the translocating polypeptide chain. In surprising contrast, cholesterol enhanced the translocation of hydrophobic sequences through the translocon. On the basis of these findings, we propose that membrane cholesterol greatly affects partitioning of hydrophobic segments into the membrane and impedes the movement of positive charges.