ArticleBiophysical journal2019
Kinetic Stability of Long-Lived Human Lens γ-Crystallins and Their Isolated Double Greek Key Domains.
Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 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
- Mimicking oxidative damage in γS-crystallin with site-specific incorporation of 5-hydroxytryptophan.Biophysical reports · 2026Article
- Enzyme-free biochemical production of seamlessly N-to-C cyclized peptides from natural or recombinant proteins.bioRxiv : the preprint server for biology · 2025Article
- Cataract-prone variants of γD-crystallin populate a conformation with a partially unfolded N-terminal domain under native conditions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Enzyme-free biochemical production of seamlessly N-to-C cyclized peptides from natural or recombinant proteins.Methods in enzymology · 2025Article
- Comparative analysis of thermal adaptations of extremophilic prolyl oligopeptidases.Biophysical journal · 2024Article
- Review
- The importance of the fourth Greek key motif of human γD-crystallin in maintaining lens transparency-the tale told by the tail.Molecular vision · 2024Article
- A novel missense mutation in the CRYBA2 caused autosomal dominant presenile cataract in a Chinese family.Molecular genetics and genomics : MGG · 2023Article
- Role of Oxidative Stress in Ocular Diseases: A Balancing Act.Metabolites · 2023Review
- Network Hamiltonian Models for Unstructured Protein Aggregates, with Application to γD-Crystallin.The journal of physical chemistry. B · 2023Article
- Article
- Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
- Redox chemistry of lens crystallins: A system of cysteines.Experimental eye research · 2021Review
- 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
- Altered Protein Dynamics and Increased Aggregation of Human γS-Crystallin Due to Cataract-Associated Deamidations.Biochemistry · 2019Article
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
Abstract
The γ-crystallins of the eye lens nucleus are among the longest-lived proteins in the human body. Synthesized in utero, they must remain folded and soluble throughout adulthood to maintain lens transparency and avoid cataracts. γD- and γS-crystallin are two major monomeric crystallins of the human lens. γD-crystallin is concentrated in the oldest lens fiber cells, the lens nucleus, whereas γS-crystallin is concentrated in the younger cells of the lens cortex. The kinetic stability parameters of these two-domain proteins and their isolated domains were determined and compared. Kinetic unfolding experiments monitored by fluorescence spectroscopy in varying concentrations of guanidinium chloride were used to extrapolate unfolding rate constants and half-lives of the crystallins in the absence of the denaturant. Consistent with their long lifespans in the lens, extrapolated half-lives for the initial unfolding step were on the timescale of years. Both proteins' isolated N-terminal domains were less kinetically stable than their respective C-terminal domains at denaturant concentrations predicted to disrupt the domain interface, but at low denaturant concentrations, the relative kinetic stabilities were reversed. Cataract-associated aggregation has been shown to proceed from partially unfolded intermediates in these proteins; their extreme kinetic stability likely evolved to protect the lens from the initiation of aggregation reactions. Our findings indicate that the domain interface is the source of significant kinetic stability. The gene duplication and fusion event that produced the modern two-domain architecture of vertebrate lens crystallins may be the origin of their high kinetic as well as thermodynamic stability.
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