Structure of the Sec61 channel opened by a signal sequence

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Science  01 Jan 2016:
Vol. 351, Issue 6268, pp. 88-91
DOI: 10.1126/science.aad4992

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Seeing the signal sequence in action

Protein translocation across the endoplasmic reticulum (ER) involves the interaction of a signal sequence with the protein translocation channel. Although much work has looked at the details of protein translocation, questions remain. Voorhees and Hegde present a single-particle cryoelectron microscopy study of the mammalian ER translocation apparatus at the point in which the signal sequence is engaging the translocation pore.

Science, this issue p. 88


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.

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