Sequence determinants of folding and stability for the P22 Arc repressor dimer

Area of Science:

• Protein structure and folding
• Biophysics
• Molecular biology

Background:

• The Arc repressor is a small, homodimeric protein crucial for gene regulation.
• Understanding protein folding mechanisms is fundamental to molecular biology and disease research.

Purpose of the Study:

• To investigate the key determinants of Arc repressor protein structure and stability.
• To elucidate the characteristics of the transition state during Arc repressor folding and unfolding.

Main Methods:

• Analysis of mutant Arc repressor proteins with altered hydrophobic core residues.
• Characterization of protein folding intermediates and transition states using biophysical techniques.

Main Results:

• Hydrophobic core side chains are critical for Arc repressor structure.
• Hydrogen bonds and salt bridges contribute to stability but can be substituted by hydrophobic interactions.
• The folding transition state is dimeric with significant buried hydrophobic surface, but lacks beta-sheet formation.
• Limited side chain information is utilized in the transition state, indicating later stages for core packing and hydrogen bond optimization.

Conclusions:

• Protein structure is primarily dictated by hydrophobic interactions within the core.
• Arc repressor folding involves a late-stage optimization of specific side chain interactions and hydrogen bonding.
• The findings provide insights into the general principles of protein folding and stability.