Structure of the Sec61 channel opened by a signal sequence

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Secreted and integral membrane proteins constitute a significant portion of the proteome.
• These proteins rely on hydrophobic signals for translocation across or insertion into lipid bilayers.
• The Sec61 protein-conducting channel facilitates this process, but the mechanism of signal-induced channel opening remains unclear.

Purpose of the Study:

• To elucidate the molecular mechanism by which hydrophobic signals open the Sec61 channel.
• To determine the structure of the Sec61 channel in its active, signal-bound state.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to visualize the Sec61 channel.
• Structural analysis focused on the interaction between a signal sequence and the Sec61 channel.

Main Results:

• The structure of an active Sec61 channel opened by a signal sequence was determined.
• The signal sequence was observed to displace helix 2 of Sec61α.
• This displacement induced a conformational change, opening the central pore axially and laterally.

Conclusions:

• The study provides a structural basis for how hydrophobic signals interact with the Sec61 channel.
• A pathway is proposed for signal sequences engaging the channel to access the lipid bilayer.
• Understanding this mechanism is vital for comprehending protein transport across membranes.