ArticleThe Journal of biological chemistry2019
Structural and functional consequences of age-related isomerization in α-crystallins.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Spontaneous Isomerization of Tau is Most Prevalent in Alzheimer's Disease.NeuroMarkers · 2026Article
- Spontaneous Non-Catalyzed Molecular Reactions and Interactions in the Human Body: Biomedical Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Mimicking oxidative damage in γS-crystallin with site-specific incorporation of 5-hydroxytryptophan.Biophysical reports · 2026Article
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- Isomerized and Racemized Aspartyl and Deamidated Asparagine Residues Identified in ɣS-Crystallin.Chembiochem : a European journal of chemical biology · 2025Article
- Deep Characterization of Isomerization in the Human Eye Lens Proteome by Crystallin-Depleted Data-Independent Acquisition.Aging cell · 2025Article
- Determination of Trends Underlying Aspartic Acid Isomerization in Intact Proteins Reveals Unusually Rapid Isomerization of Tau.ACS chemical neuroscience · 2025Article
- Review
- Unusually Rapid Isomerization of Aspartic Acid in Tau.bioRxiv : the preprint server for biology · 2024Article
- Stability of Protein Pharmaceuticals: Recent Advances.Pharmaceutical research · 2024Review
- Quantification of serine residue stereoinversion in a short peptide by reversed-phase high-performance liquid chromatography: analysis of mechanisms promoting serine stereoinversion.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Article
- Probing effects of site-specific aspartic acid isomerization on structure and stability of GB1 through chemical protein synthesis.Protein science : a publication of the Protein Society · 2024Article
- Influence of Asp Isomerization on Trypsin and Trypsin-like Proteolysis.Analytical chemistry · 2022Article
- PIMT-Mediated Labeling of l-Isoaspartic Acid with Tris Facilitates Identification of Isomerization Sites in Long-Lived Proteins.Journal of the American Society for Mass Spectrometry · 2022Article
- Understanding and controlling amyloid aggregation with chirality.Current opinion in chemical biology · 2021Review
- Association of Alpha-Crystallin with Fiber Cell Plasma Membrane of the Eye Lens Accompanied by Light Scattering and Cataract Formation.Membranes · 2021Review
- α-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones.Annual review of physical chemistry · 2021Review
- Chemical Properties Determine Solubility and Stability in βγ-Crystallins of the Eye Lens.Chembiochem : a European journal of chemical biology · 2021Review
- Imbalances in the eye lens proteome are linked to cataract formation.Nature structural & molecular biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Long-lived proteins are subject to spontaneous degradation and may accumulate a range of modifications over time, including subtle alterations such as side-chain isomerization. Recently, tandem MS has enabled identification and characterization of such peptide isomers, including those differing only in chirality. However, the structural and functional consequences of these perturbations remain largely unexplored. Here, we examined the impact of isomerization of aspartic acid or epimerization of serine at four sites mapping to crucial oligomeric interfaces in human αA- and αB-crystallin, the most abundant chaperone proteins in the eye lens. To characterize the effect of isomerization on quaternary assembly, we utilized synthetic peptide mimics, enzyme assays, molecular dynamics calculations, and native MS experiments. The oligomerization of recombinant forms of αA- and αB-crystallin that mimic isomerized residues deviated from native behavior in all cases. Isomerization also perturbs recognition of peptide substrates, either enhancing or inhibiting kinase activity. Specifically, epimerization of serine (αASer-162) dramatically weakened inter-subunit binding. Furthermore, phosphorylation of αBSer-59, known to play an important regulatory role in oligomerization, was severely inhibited by serine epimerization and altered by isomerization of nearby αBAsp-62. Similarly, isomerization of αBAsp-109 disrupted a vital salt bridge with αBArg-120, a contact that when broken has previously been shown to yield aberrant oligomerization and aggregation in several disease-associated variants. Our results illustrate how isomerization of amino acid residues, which may seem to be only a minor structural perturbation, can disrupt native structural interactions with profound consequences for protein assembly and activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.