Stability of Protein-Specific Hydration Shell on Crowding.

Area of Science:

• Biophysics
• Structural Biology
• Ocular Science

Background:

• Protein crowding significantly impacts biological systems.
• The human eye lens relies on transparent hydrogels formed by γS-crystallin (γS-WT).
• A mutation (γS-G18V) alters lens properties, offering a model for studying crowding effects.

Purpose of the Study:

• Investigate how protein crowding affects hydration water diffusion dynamics.
• Determine if hydrogel formation in γS-WT causes a single water population or coexistence of bulk and hydration water.
• Understand the role of hydration shell stability in protein function and disease.

Main Methods:

• Utilized localized spin probes to measure translational diffusivity of water.
• Examined both surface hydration water and interstitial water.
• Compared wild-type γS-crystallin (γS-WT) with a cataract-related mutant (γS-G18V) across various concentrations.

Main Results:

• γS-WT hydration shells remain dynamic even at high concentrations (500 mg/mL), with a robust surface water population coexisting with bulk-like water.
• Protein crowding in γS-WT increases surface hydration water but does not eliminate bulk water.
• γS-G18V exhibits irreversible dehydration of surface water under moderate concentration changes.

Conclusions:

• The stability of the protein-specific hydration shell is critical for the effects of protein crowding.
• γS-crystallin's function in the eye lens likely depends on its ability to maintain a stable hydration shell.
• The G18V mutation disrupts this crucial hydration shell stability, leading to altered lens properties.