Voorhees Rebecca M, Hegde Ramanujan S
MRC Laboratory of Molecular Biology, Medical Research Council, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Science. 2016 Jan 1;351(6268):88-91. doi: 10.1126/science.aad4992.
Secreted and integral membrane proteins compose 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 of how hydrophobic signals within a nascent polypeptide trigger channel opening is not understood. Here, we used cryo-electron 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, which triggers a rotation that opens the central pore both axially across the membrane and laterally toward the lipid bilayer. Comparisons with structures of Sec61 in other states suggest a pathway for how hydrophobic signals engage the channel to gain access to the lipid bilayer.
分泌蛋白和整合膜蛋白构成了生物蛋白质组的三分之一。这些蛋白质含有疏水信号，可通过Sec61蛋白质传导通道引导它们跨脂质双层转运或插入脂质双层。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，我们使用冷冻电子显微镜来确定由信号序列打开的活性Sec61通道的结构。该信号取代了Sec61α的螺旋2，从而引发旋转，使中央孔在膜的轴向和横向朝着脂质双层打开。与其他状态下的Sec61结构进行比较，揭示了疏水信号与通道结合以进入脂质双层的途径。
