ArticleThe Journal of biological chemistry2016
Single-molecule Force Spectroscopy Predicts a Misfolded, Domain-swapped Conformation in human γD-Crystallin Protein.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 48 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
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.bioRxiv : the preprint server for biology · 2026Article
- Adjacent domains drive the emergence of misfolded intermediates in the folding pathway of the PDZ4 from MAGI1.BBA advances · 2026Article
- Article
- 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
- Single-molecule magnetic tweezers to probe the equilibrium dynamics of individual proteins at physiologically relevant forces and timescales.Nature protocols · 2024Review
- A Single-Molecule Strategy to Capture Non-native Intramolecular and Intermolecular Protein Disulfide Bridges.Nano letters · 2022Article
- Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
- Single-molecule optical tweezers reveals folding steps of the domain swapping mechanism of a protein.Biophysical journal · 2021Article
- 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
- Intrinsically Disordered Regions of the DNA-Binding Domain of Human FoxP1 Facilitate Domain Swapping.Journal of molecular biology · 2020Article
- [Resonance light scattering spectroscopy can directly characterize protein solubility].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes.Frontiers in molecular biosciences · 2020Review
- Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family.Journal of ophthalmology · 2020Article
- Tandem domain swapping: determinants of multidomain protein misfolding.Current opinion in structural biology · 2019Review
- Kinetic Stability of Long-Lived Human Lens γ-Crystallins and Their Isolated Double Greek Key Domains.Biophysical journal · 2019Article
- Dynamic disulfide exchange in a crystallin protein in the human eye lens promotes cataract-associated aggregation.The Journal of biological chemistry · 2018Article
- Spontaneous refolding of the large multidomain protein malate synthase G proceeds through misfolding traps.The Journal of biological chemistry · 2018Article
- Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH.Nature communications · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cataract is a protein misfolding disease where the size of the aggregate is directly related to the severity of the disorder. However, the molecular mechanisms that trigger the onset of aggregation remain unknown. Here we use a combination of protein engineering techniques and single-molecule force spectroscopy using atomic force microscopy to study the individual unfolding pathways of the human γD-crystallin, a multidomain protein that must remain correctly folded during the entire lifetime to guarantee lens transparency. When stretching individual polyproteins containing two neighboring HγD-crystallin monomers, we captured an anomalous misfolded conformation in which the β1 and β2 strands of the N terminus domain of two adjacent monomers swap. This experimentally elusive domain-swapped conformation is likely to be responsible for the increase in molecular aggregation that we measure in vitro. Our results demonstrate the power of force spectroscopy at capturing rare misfolded conformations with potential implications for the understanding of the molecular onset of protein aggregation.
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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.