Summary & Purpose

a-Crystallin (aABc) is a major protein comprised of aA-crystallin (aAc) and aB-crystallin (aBc) that is found in the human eye lens and works as a molecular chaperone by preventing the aggregation of proteins and providing tolerance to stress. However, with age and cataract formation, the concentration of aABc in the eye lens cytoplasm decreases, with a corresponding increase in the membrane-bound aABc. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the role of cholesterol (Chol) and Chol bilayer domains (CBDs) in the binding of aAc, aBc, and aABc to the Chol/model of human lens-lipid (Chol/MHLL) membranes. The maximum percentage of membrane surface occupied (MMSO) by aAc, aBc, and aABc to Chol/MHLL membranes at a mixing ratio of 0 followed the trends: MMSO (aAc) > MMSO (aBc) ˜ MMSO (aABc), indicating that a higher amount of aAc binds to these membranes compared to aBc and aABc. However, with an increase in the Chol concentration in the Chol/MHLL membranes, the MMSO by aAc, aBc, and aABc decreases until it is completely diminished at a mixing ratio of 1.5. The Ka of aAc, aBc, and aABc to Chol/MHLL membranes at a mixing ratio of 0 followed the trend: Ka (aBc) ˜ Ka (aABc) > Ka (aAc), but it was close to zero with the diminished binding at a Chol/MHLL mixing ratio of 1.5. The mobility near the membrane headgroup regions decreased with aAc, aBc, and aABc binding, and the Chol antagonized the capacity of the aAc, aBc, and aABc to decrease mobility near the headgroup regions. No significant change in membrane order near the headgroup regions was observed, with an increase in aAc, aBc, and aABc concentrations. Our results show that aAc, aBc, and aABc bind differently with Chol/MHLL membranes at mixing ratios of 0 and 0.5, decreasing the mobility and increasing hydrophobicity near the membrane headgroup region, likely forming the hydrophobic barrier for the passage of polar and ionic molecules, including antioxidants (glutathione), creating an oxidative environment inside the lens, leading to the development of cataracts. However, all binding was completely diminished at a mixing ratio of 1.5, indicating that high Chol and CBDs inhibit the binding of aAc, aBc, and aABc to membranes, preventing the formation of hydrophobic barriers and likely protecting against cataract formation.

Author Identifier

Raju Timsina, ORCID: 0000-0002-3790-8472
Geraline Torssi-Torres, ORCID: 0000-0002-1690-1562
Nawal K. Khadka, ORCID: 0000-0002-2404-3799
Laxman Mainali, ORCID: 0000-0002-9570-9041

Date of Publication or Submission

4-3-2025

DOI

https://doi.org/10.18122/biophysics_data.1.boisestate

Funding Citation

The research reported in this publication was supported by the National Eye Institute of the National Institutes of Health, under Award Number R01 EY030067. Support was provided, in part, by the National Institutes of Health, NIGMS, under grant numbers P20GM103408 and P20GM109095, and the Biomolecular Research Center, RRID:SCR_019174, at Boise State University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Single Dataset or Series?

Series

Data Format

*.xlsx; *.txt

File Size

102KB

Data Attributes

See README file

Time Period

2021-2024

Update Frequency

Other

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