Evidence map›Paper›PMID 40323268›Full record

ArticleInvestigative ophthalmology & visual science2025

Cholesterol and Q147E Deamidation Modulates αA-Crystallin Membrane Binding Elucidating Protective Role of Lens Membrane Composition Changes With Aging.

Preston Hazen, Nawal K Khadka, Laxman Mainali

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Preston HazenBiomolecular Sciences Graduate Program, Boise State University, Boise, Idaho, United States.
Nawal K KhadkaDepartment of Physics, Boise State University, Boise, Idaho, United States.
Laxman MainaliBiomolecular Sciences Graduate Program, Boise State University, Boise, Idaho, United States.

Funding

Interaction of alpha-crystallin with cholesterol bilayer domains in cataract formationR01EY030067 · NEI · BOISE STATE UNIVERSITY · PI Laxman Mainali · 2019 to 2026
$2.6M
NEI NIH HHS R01 EY030067
6 · The paper itself

Abstract

Purpose: The αA-Crystallin (αAc) binding with lens membranes increases with age and cataract formation. However, the role of lipids and cholesterol (Chol) in Q147E-αAc membrane binding remains unclear, which we aim to elucidate in this study. Methods: We have used the electron paramagnetic resonance spin-labeling method to probe the Chol/ 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and Chol/ sphingomyelin (SM) membranes binding with wild-type (WT) and Q147E-αAc. Results: Compared to WT-αAc, the Q147E mutant had increased binding to POPC and decreased binding to SM membranes without Chol. Adding 33 mol% Chol to the POPC and SM membranes decreased the binding of WT and, to a lesser degree, decreased the binding of Q147E-αAc to the membranes. Adding 60 mol% Chol completely inhibited Q147E mutant and WT binding to POPC membranes. However, 33 and 60 mol% Chol completely inhibited WT and Q147E mutant binding to SM membranes, respectively. WT and Q147E-αAc membrane binding decreased membrane mobility while increasing order and hydrophobicity near the headgroup. Conclusions: In Chol-free membranes, the deamidated Q147E-αAc binds significantly more to the POPC membranes compared to WT, whereas WT binds significantly more to the SM membranes compared to Q147E-αAc. In contrast, for 33 mol% Chol-containing membranes, the deamidated Q147E-αAc binds significantly more to POPC and SM membranes than WT. Conversely, 60 mol% Chol-containing membranes completely inhibit WT and deamidated Q147E-αAc binding to POPC and SM membranes. These results suggest that increased Chol content of the lens membranes during aging protects against accumulation of modified proteins on the membrane associated with cataracts.

Indexed as

Agingalpha-Crystallin A ChainCataractCell MembraneCholesterolLens, CrystallineAnimalsElectron Spin Resonance SpectroscopyHumansPhosphatidylcholinesProtein BindingSphingomyelins1-palmitoyl-2-oleoylphosphatidylcholinealpha-Crystallin A ChainCholesterolPhosphatidylcholinesSphingomyelins

Identifiers

PMID40323268
PMCPMC12060060

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.