Molecular basis of coiled-coil formation

Area of Science:

• Protein structure and folding
• Biophysics
• Molecular biology

Background:

• Coiled coils are protein structures with diverse applications.
• Understanding coiled-coil folding mechanisms is essential for protein design.
• Trigger sequences are critical for initiating coiled-coil formation.

Purpose of the Study:

• To identify and characterize the molecular determinants of the trigger sequence helix in the GCN4 coiled coil's folding intermediate.
• To elucidate the role of these determinants in coiled-coil formation and stability.

Main Methods:

• Multidisciplinary approach combining biophysical and biochemical techniques.
• Characterization of the monomeric early folding intermediate.
• Analysis of hydrogen-bonding and electrostatic interactions.

Main Results:

• A network of hydrogen-bonding and electrostatic interactions stabilizes the trigger-sequence helix.
• This interaction network is rearranged in the final dimeric coiled coil.
• Destabilization of this network significantly impedes GCN4 leucine zipper folding.

Conclusions:

• The findings provide a molecular-level explanation for coiled-coil formation.
• Specific interactions within the trigger sequence are critical for initiating and stabilizing coiled-coil structures.
• This knowledge advances the design principles for coiled-coil based proteins.