ArticleJournal of molecular biology2010
A single destabilizing mutation (F9S) promotes concerted unfolding of an entire globular domain in gammaS-crystallin.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- The calcium signal regulatory network and the roles of calcium-binding proteins in bacteria.World journal of microbiology & biotechnology · 2026Review
- Candidate Genes for Non-Syndromic Pediatric Cataracts.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- ATP-dependent thermoring basis for the heat unfolding of the first nucleotide-binding domain isolated from human CFTR.Research square · 2024Article
- Review
- Acquired Disorder and Asymmetry in a Domain-Swapped Model for γ-Crystallin Aggregation.Journal of molecular biology · 2022Article
- 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
- A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin.Molecular and cellular biochemistry · 2018Article
- Amyloid β-Sheet Secondary Structure Identified in UV-Induced Cataracts of Porcine Lenses using 2D IR Spectroscopy.Journal of molecular biology · 2017Article
- 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
- γ-Crystallins of the chicken lens: remnants of an ancient vertebrate gene family in birds.The FEBS journal · 2016Article
- Wild-type human γD-crystallin promotes aggregation of its oxidation-mimicking, misfolding-prone W42Q mutant.The Journal of biological chemistry · 2015Article
- Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases.Chemical reviews · 2014Review
- The βγ-crystallins: native state stability and pathways to aggregation.Progress in biophysics and molecular biology · 2014Review
- Solution properties of γ-crystallins: compact structure and low frictional ratio are conserved properties of diverse γ-crystallins.Protein science : a publication of the Protein Society · 2014Article
- Structure and dynamics of the fish eye lens protein, γM7-crystallin.Biochemistry · 2013Article
- The human W42R γD-crystallin mutant structure provides a link between congenital and age-related cataracts.The Journal of biological chemistry · 2013Article
- A role for γS-crystallin in the organization of actin and fiber cell maturation in the mouse lens.The FEBS journal · 2012Article
- Protein misfolding and aggregation in cataract disease and prospects for prevention.Trends in molecular medicine · 2012Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Conformational change and aggregation of native proteins are associated with many serious age-related and neurological diseases. gammaS-Crystallin is a highly stable, abundant structural component of vertebrate eye lens. A single F9S mutation in the N-terminal domain of mouse gammaS-crystallin causes the severe Opj cataract, with disruption of cellular organization and appearance of fibrillar structures in the lens. Although the mutant protein has a near-native fold at room temperature, significant increases in hydrogen/deuterium exchange rates were observed by NMR for all the well-protected beta-sheet core residues throughout the entire N-terminal domain of the mutant protein, resulting in up to a 3.5-kcal/mol reduction in the free energy of the folding/unfolding equilibrium. No difference was detected for the C-terminal domain. At a higher temperature, this effect further increases to allow for a much more uniform exchange rate among the N-terminal core residues and those of the least well-structured surface loops. This suggests a concerted unfolding intermediate of the N-terminal domain, while the C-terminal domain stays intact. Increasing concentrations of guanidinium chloride produced two transitions for the Opj mutant, with an unfolding intermediate at approximately 1 M guanidinium chloride. The consequence of this partial unfolding, whether by elevated temperature or by denaturant, is the formation of thioflavin T staining aggregates, which demonstrated fibril-like morphology by atomic force microscopy. Seeding with the already unfolded protein enhanced the formation of fibrils. The Opj mutant protein provides a model for stress-related unfolding of an essentially normally folded protein and production of aggregates with some of the characteristics of amyloid fibrils.
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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.