Pressure-dependent changes in the solution structure of hen egg-white lysozyme

Area of Science:

• Structural Biology
• Biophysics
• Protein Dynamics

Background:

• Understanding protein structure and stability is crucial but challenging.
• Proteins functioning under extreme conditions offer insights into physical constraints.
• Protein behavior under high pressure remains largely unexplored due to technical limitations.

Purpose of the Study:

• To develop novel methodology for calculating protein structure changes under varying pressure.
• To investigate the pressure-induced structural alterations in lysozyme in solution.
• To provide the first solution structure of a globular protein under high pressure.

Main Methods:

• Utilized Nuclear Magnetic Resonance (NMR) chemical shift changes to monitor structural modifications.
• Developed new computational methods for analyzing pressure-induced structural changes in solution.
• Examined lysozyme structure at pressures ranging from 30 bar to 2000 bar.

Main Results:

• The alpha-helical domain of lysozyme compressed by approximately 1% due to enhanced helix packing.
• The beta-sheet domain showed minimal compression but increased structural distortion compared to the alpha-domain.
• Significant volume changes were observed near hydrated cavities, indicating their role in pressure response.

Conclusions:

• High pressure induces distinct structural changes in different domains of lysozyme.
• Buried water molecules are critical for conformational fluctuations at ambient pressures.
• Hydrated cavities act as nucleation sites for pressure-induced denaturation and channel opening.