ArticleProceedings of the National Academy of Sciences of the United States of America2011
Cataract-associated mutant E107A of human gammaD-crystallin shows increased attraction to alpha-crystallin and enhanced light scattering.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 57 citations in OpenAlex.
- Human Crystallin Variation and Cataract.Investigative ophthalmology & visual science · 2026Review
- Atomistic modeling of liquid-liquid phase equilibrium explains dependence of critical temperature on γ-crystallin sequence.Communications biology · 2023Article
- Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence.bioRxiv : the preprint server for biology · 2023Article
- Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a γD-Crystallin Mutant.Biophysical journal · 2019Article
- Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation.Chemical reviews · 2018Review
- Model for screened, charge-regulated electrostatics of an eye lens protein: Bovine gammaB-crystallin.Physical review. E · 2017Article
- A Combined NMR and SAXS Analysis of the Partially Folded Cataract-Associated V75D γD-Crystallin.Biophysical journal · 2017Article
- Statistical-thermodynamic model for light scattering from eye lens protein mixtures.The Journal of chemical physics · 2017Article
- Expression of Cataract-linked γ-Crystallin Variants in Zebrafish Reveals a Proteostasis Network That Senses Protein Stability.The Journal of biological chemistry · 2016Article
- Modeling phase transitions in mixtures of β-γ lens crystallins.Soft matter · 2016Article
- Nuclear Magnetic Resonance Structure of a Major Lens Protein, Human γC-Crystallin: Role of the Dipole Moment in Protein Solubility.Biochemistry · 2016Article
- Aggregation of Trp > Glu point mutants of human gamma-D crystallin provides a model for hereditary or UV-induced cataract.Protein science : a publication of the Protein Society · 2016Article
- Functional sequences in human alphaB crystallin.Biochimica et biophysica acta · 2016Review
- The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.PloS one · 2016Article
- Deamidation of Human γS-Crystallin Increases Attractive Protein Interactions: Implications for Cataract.Biochemistry · 2015Article
- Molecular mechanism of the chaperone function of mini-α-crystallin, a 19-residue peptide of human α-crystallin.Biochemistry · 2015Article
- Hard sphere-like glass transition in eye lens α-crystallin solutions.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The βγ-crystallins: native state stability and pathways to aggregation.Progress in biophysics and molecular biology · 2014Review
- The cataract-associated V41M mutant of human γS-crystallin shows specific structural changes that directly enhance local surface hydrophobicity.Biochemical and biophysical research communications · 2014Article
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5 authors at 2 institutions in 1 country.
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Abstract
Several point mutations in human γD-crystallin (HGD) are now known to be associated with cataract. So far, the in vitro studies of individual mutants of HGD alone have been sufficient in providing plausible molecular mechanisms for the associated cataract in vivo. Nearly all the mutant proteins in solution showed compromised solubility and enhanced light scattering due to altered homologous γ-γ crystallin interactions. In sharp contrast, here we present an intriguing case of a human nuclear cataract-associated mutant of HGD--namely Glu107 to Ala (E107A), which is nearly identical to the wild type in structure, stability, and solubility properties, with one exception: Its pI is higher by nearly one pH unit. This increase dramatically alters its interaction with α-crystallin. There is a striking difference in the liquid-liquid phase separation behavior of E107A-α-crystallin mixtures compared to HGD-α-crystallin mixtures, and the light-scattering intensities are significantly higher for the former. The data show that the two coexisting phases in the E107A-α mixtures differ much more in protein density than those that occur in HGD-α mixtures, as the proportion of α-crystallin approaches that in the lens nucleus. Thus in HGD-α mixtures, the demixing of phases occurs primarily by protein type while in E107A-α mixtures it is increasingly governed by protein density. Analysis of these results suggests that the cataract due to the E107A mutation could result from the instability caused by the altered attractive interactions between dissimilar proteins--i.e., heterologous γ-α crystallin interactions--primarily due to the change in surface electrostatic potential in the mutant protein.
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