Water: foldase activity in catalyzing polypeptide conformational rearrangements

Area of Science:

• Biophysics
• Protein dynamics
• Biochemistry

Background:

• Polypeptide conformation is crucial for protein function.
• Understanding protein folding in nonpolar environments, like lipid bilayers, is essential.
• The role of water in modulating protein dynamics in hydrophobic regions is not fully understood.

Purpose of the Study:

• To investigate the effect of water concentration on polypeptide conformer interconversion in a low dielectric medium.
• To elucidate the mechanism by which water influences this process.
• To assess the potential of water to act as a catalytic agent in protein folding.

Main Methods:

• Studied polypeptide conformer interconversion in a low dielectric environment with varying water concentrations.
• Quantified the rate of interconversion, specifically the transition of a parallel gramicidin dimer to an antiparallel dimer.
• Analyzed the cooperative nature of the process using Hill coefficient analysis.

Main Results:

• Water concentration significantly affects polypeptide conformer interconversion rate, increasing it by up to 10^3.
• Water appears to catalyze hydrogen bond exchange, mimicking the function of a foldase.
• A high Hill coefficient of 6.5 indicates a highly cooperative interconversion process.

Conclusions:

• Water acts as a catalyst for polypeptide conformer interconversion in low dielectric environments.
• The scarcity of water in nonpolar biological regions, such as protein hydrophobic cores or lipid bilayers, may limit and control protein folding rates.
• These findings highlight the critical role of localized water availability in protein dynamics and function.