Structure of the Sec61 channel opened by a signal sequence.
Structure of the Sec61 channel opened by a signal sequence.
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DOI：
10.1126/science.aad4992
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Hegde RS
中科院分区：
文献类型：
--
作者：
Voorhees RM;Hegde RS
分泌的和完整的膜蛋白占生物蛋白质组的三分之一。这些蛋白质含有疏水信号，通过Sec61蛋白传导通道引导它们穿过或插入到脂质双层中。新生多肽中的疏水信号如何触发通道开放的分子基础尚不清楚。在这里，我们使用电子冷冻显微镜来确定已经被信号序列打开的活跃的Sec61通道的结构。该信号取代了Sec61α的螺旋2，触发了一种旋转，使中央孔在轴向穿过膜和横向朝向脂质双层打开。与其他状态下Sec61的结构比较表明，疏水信号如何与通道接触以获得脂质双层。
Secreted and integral membrane proteins comprise up to one-third of the biological proteome. These proteins contain hydrophobic signals that direct their translocation across or insertion into the lipid bilayer by the Sec61 protein conducting channel. The molecular basis for how hydrophobic signals within a nascent polypeptide trigger channel opening is not understood. Here, we use electron cryo-microscopy to determine the structure of an active Sec61 channel that has been opened by a signal sequence. The signal supplants helix 2 of Sec61α, triggering a rotation that opens the central pore both axially across the membrane and laterally toward the lipid bilayer. Comparisons to structures of Sec61 in other states suggest a pathway for how hydrophobic signals engage the channel to gain access to the lipid bilayer.