Summary & Purpose

Purpose: αA-crystallin (αAc), the predominant subunit comprising α-crystallin (αABc), becomes increasingly deamidated and membrane bound with cataract formation. Furthermore, the lens lipids and cholesterol (Chol) composition significantly change with age and cataract formation. Despite this, the relationship between αAc deamidation and lens membrane composition in cataractogenesis remains unclear. To address this, we analyzed the role of N101 deamidation and membrane composition in the membrane interactions of αAc.

Methods: Experimentation involved using electron paramagnetic resonance (EPR) to analyze wild-type (WT) and N101D-αAc membrane binding and its physical effects on the membrane properties of 60-year-old (yo) and 20-yo model human lens lipid (MHLL) membranes containing 2 mol% cholestane spin label and increasing Chol concentrations.

Results: Without Chol, WT-αAc and N101D-αAc do not significantly differ in their 60-yo MHLL membrane binding, but N101D deamidation significantly diminishes αAc binding in 20-yo MHLL membranes. With Chol, the binding of WT-αAc and N101D-αAc to 60-yo and 20-yo MHLL membranes is significantly reduced. However, N101D-αAc consistently binds less and with a lower affinity than WT-αAc to both membranes at all Chol contents. Additionally, both WT-αAc and N101D-αAc membrane binding decreases 60-yo and 20-yo MHLL membrane mobility while increasing hydrophobicity and order near the headgroup region.

Conclusions: These data indicate that lens membrane composition significantly modulates the membrane association of WT-αAc and N101D-αAc while N101D deamidation generally diminishes αAc membrane binding regardless of membrane composition. Consequently, it appears that N101D deamidation may synchronously function with the membrane composition alterations to diminish αAc membrane binding throughout life and prevent cataract formation.

Author Identifier

Nawal K. Khadka, ORCID: 0000-0002-2404-3799

Laxman Mainal, ORCID: 0000-0002-9570-9041

Date of Publication or Submission

10-30-2026

DOI

https://doi.org/10.18122/biophysics_data.9.boisestate

Funding Citation

Supported by a grant from the National Eye Institute and National Institute of General Medical Sciences, National Institutes of Health (R01EY030067 via IDeA co-funding). The content of this manuscript is solely the responsibility of the authors and is not necessarily representative of the official views of the National Institutes of Health.

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Series

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*.xlsx; *.txt

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46.8 KB

Data Attributes

Data collection and analysis are explained in the published manuscript. See Publications Related to This Data section.

Time Period

2024-2026

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