Cavities and Excited States in Proteins

Area of Science:

• Biophysics
• Structural Biology
• Protein Dynamics

Background:

• Protein cavities (voids) are structural defects impacting protein dynamics and function.
• The origin and mechanisms of protein cavities remain largely elusive.
• High-pressure NMR spectroscopy offers insights into protein behavior under pressure.

Purpose of the Study:

• To review recent studies on protein cavities using high-pressure NMR spectroscopy.
• To elucidate the relationship between protein cavities, pressure response, and protein dynamics.
• To explore the role of cavities in protein function and evolution.

Main Methods:

• Analysis of pressure-dependent chemical shifts using NMR spectroscopy.
• Characterization of protein cavities and their density.
• Investigating hen lysozyme as a model system for cavity hydration and water penetration.

Main Results:

• Proteins exhibit both linear (native ensemble compression) and non-linear (excited states) responses to pressure.
• Non-linear pressure shifts are common in globular proteins and correlate with cavity density.
• Cavity hydration and water penetration drive conformational transitions to excited states in hen lysozyme.
• Transient cavities, formed by motions like aromatic ring flips, reflect intrinsic protein dynamics.

Conclusions:

• Protein cavities are integral to protein dynamics, function, and evolution.
• Cavity hydration and water penetration are key mechanisms for protein conformational changes.
• Both equilibrium and transient cavities contribute to the dynamic nature of proteins.