TRAP mediated conformational changes of the human Sec61 channel

Area of Science:

• Molecular biology
• Structural biology
• Biophysics

Background:

• Sec61 is an integral membrane pore essential for protein translocation into the endoplasmic reticulum.
• The TRAP complex is an accessory protein required for efficient translocation of precursor proteins with weak signal peptides.
• Previous studies show TRAP interacts with Sec61, but its precise mechanism remains unclear.

Purpose of the Study:

• To elucidate the mechanism by which TRAP supports protein translocation mediated by Sec61.
• To investigate the structural consequences of TRAP binding on the Sec61 complex.

Main Methods:

• Atomistic molecular dynamics simulations were employed to model the Sec61-TRAP interaction.
• Analysis focused on the conformational changes within the Sec61 complex upon TRAP binding.

Main Results:

• TRAP binding was shown to maintain Sec61 in a partially opened state.
• Looser packing of Sec61 transmembrane helices and a shifted plug helix were observed.
• TRAP stabilized an open conformation of the Sec61 lateral gate and pore ring.

Conclusions:

• TRAP binding facilitates Sec61 opening, supporting the translocation of precursor proteins with weak signal peptides.
• The findings provide mechanistic insights into TRAP's role in protein transport.
• This study corroborates and refines existing models of TRAP-assisted protein translocation.