ArticleBiochemistry2020
Human γS-Crystallin-Copper Binding Helps Buffer against Aggregation Caused by Oxidative Damage.
Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.The Journal of biological chemistry · 2026Article
- Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.npj aging · 2026Review
- The Eye Lens Protein, γS Crystallin, Undergoes Glutathionylation-Induced Disulfide Bonding Between Cysteines 22 and 26.Biomolecules · 2025Article
- Characterization of the Interaction of Human γS Crystallin with Metal Ions and Its Effect on Protein Aggregation.Biomolecules · 2024Article
- Aging of the eye: Lessons from cataracts and age-related macular degeneration.Ageing research reviews · 2024Review
- Review
- Copper binding and protein aggregation: a journey from the brain to the human lens.RSC chemical biology · 2023Article
- ATCUN-like Copper Site in βB2-Crystallin Plays a Protective Role in Cataract-Associated Aggregation.Inorganic chemistry · 2023Article
- Role of Oxidative Stress in Ocular Diseases: A Balancing Act.Metabolites · 2023Review
- Manipulating polydispersity of lens β-crystallins using divalent cations demonstrates evidence of calcium regulation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Zinc and Copper Ions Induce Aggregation of Human β-Crystallins.Molecules (Basel, Switzerland) · 2022Article
- Deamidation of the human eye lens protein γS-crystallin accelerates oxidative aging.Structure (London, England : 1993) · 2022Article
- Human γS-Crystallin Resists Unfolding Despite Extensive Chemical Modification from Exposure to Ionizing Radiation.The journal of physical chemistry. B · 2022Article
- Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina.Antioxidants (Basel, Switzerland) · 2021Article
- Redox chemistry of lens crystallins: A system of cysteines.Experimental eye research · 2021Review
- A simple vapor-diffusion method enables protein crystallization inside the HARE serial crystallography chip.Acta crystallographica. Section D, Structural biology · 2021Article
- Protamine Characterization by Top-Down Proteomics: Boosting Proteoform Identification with DBSCAN.Proteomes · 2021Article
- Chemical Properties Determine Solubility and Stability in βγ-Crystallins of the Eye Lens.Chembiochem : a European journal of chemical biology · 2021Review
- Cumulative deamidations of the major lens protein γS-crystallin increase its aggregation during unfolding and oxidation.Protein science : a publication of the Protein Society · 2020Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Divalent metal cations can play a role in protein aggregation diseases, including cataract. Here we compare the aggregation of human γS-crystallin, a key structural protein of the eye lens, via mutagenesis, ultraviolet light damage, and the addition of metal ions. All three aggregation pathways result in globular, amorphous-looking structures that do not elongate into fibers. We also investigate the molecular mechanism underlying copper(II)-induced aggregation. This work was motivated by the observation that zinc(II)-induced aggregation of γS-crystallin is driven by intermolecular bridging of solvent-accessible cysteine residues, while in contrast, copper(II)-induced aggregation of this protein is exacerbated by the removal of solvent-accessible cysteines via mutation. Here we find that copper(II)-induced aggregation results from a complex mechanism involving multiple interactions with the protein. The initial protein-metal interactions result in the reduction of Cu(II) to Cu(I) with concomitant oxidation of γS-crystallin. In addition to the intermolecular disulfides that represent a starting point for aggregation, intramolecular disulfides also occur in the cysteine loop, a region of the N-terminal domain that was previously found to mediate the early stages of cataract formation. This previously unobserved ability of γS-crystallin to transfer disulfides intramolecularly suggests that it may serve as an oxidation sink for the lens after glutathione levels have become depleted during aging. γS-Crystallin thus serves as the last line of defense against oxidation in the eye lens, a result that underscores the chemical functionality of this protein, which is generally considered to play a purely structural role.
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