Age-Related Lens Membrane Composition and N101D Deamidation Modulate αA-Crystallin Membrane Interactions Relevant to Cataract.
- 1Biomolecular Sciences Graduate Program, Boise State University, Boise, Idaho, United States.
- 2Department of Physics, Boise State University, Boise, Idaho, United States.
Abstract
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.
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BibTeX
@article{hazen2026agerelated,
title = {{Age-Related Lens Membrane Composition and N101D Deamidation Modulate αA-Crystallin Membrane Interactions Relevant to Cataract.}},
author = {Preston Hazen and Jordyn Anderson and Navdeep Kalkat and Binod Aryal and Nawal K Khadka and Laxman Mainali},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.18},
url = {https://europepmc.org/article/MED/42847596},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Age-Related Lens Membrane Composition and N101D Deamidation Modulate αA-Crystallin Membrane Interactions Relevant to Cataract.
AU - Preston Hazen
AU - Jordyn Anderson
AU - Navdeep Kalkat
AU - Binod Aryal
AU - Nawal K Khadka
AU - Laxman Mainali
PY - 2026
DA - 2026/10/01
JO - Investigative ophthalmology & visual science
DO - 10.1167/iovs.67.12.18
UR - https://europepmc.org/article/MED/42847596
AB - 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.
SN - 0146-0404
SN - 1552-5783
ER -