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Structure of the Sec61 channel opened by a signal sequence.

ABSTRACT: 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 Sec61?, 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.

SUBMITTER: Voorhees RM

PROVIDER: S-EPMC4700591 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Structure of the Sec61 channel opened by a signal sequence.

Voorhees Rebecca M RM Hegde Ramanujan S RS

Science (New York, N.Y.) 20160101 6268

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 sequ ...[more]

PMID: 26721998

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