Hydrophobicity and signal sequence binding to the Sec complex: A single molecule biophysical perspective

Area of Science:

• Molecular Biology
• Cell Biology
• Biophysics

Background:

• The Sec61 complex is essential for protein translocation into the endoplasmic reticulum (ER).
• Signal sequences (SSs) with low hydrophobicity require assistance for Sec61 channel opening.
• Understanding SS-Sec61 interactions is crucial for ER-associated diseases.

Purpose of the Study:

• Investigate the effect of signal sequence (SS) hydrophobicity on Sec complex interaction.
• Analyze SS-Sec complex binding dynamics at the single-molecule level.

Main Methods:

• Utilized optical tweezers for single-molecule force spectroscopy.
• Examined three SSs with varying hydrophobicity (low, moderate, high).

Main Results:

• Highly hydrophobic SSs exhibited shorter interaction times and lower energy barriers with the Sec complex.
• Less hydrophobic SSs showed more stable interactions with longer binding durations.
• Hydrophobicity influences the stability of SS binding to the Sec complex.

Conclusions:

• The Sec complex may selectively bind SSs based on their hydrophobicity.
• Findings provide insights into SS translocation mechanisms and ER-associated diseases.