ArticleProceedings of the National Academy of Sciences of the United States of America2014
Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 47 citations in OpenAlex.
- High-Resolution Optical Chromatography: Principles, Innovations, and Emerging Biomedical Applications.Micromachines · 2026Review
- Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.JACS Au · 2026Article
- DNA origami-enhanced force spectroscopy and AlphaFold structural analyses reveal the folding landscape of calcium-binding proteins.Science advances · 2025Article
- Mechanical properties of human tumour tissues and their implications for cancer development.Nature reviews. Physics · 2024Article
- Investigation of metal ion binding biomolecules one molecule at a time.Frontiers in chemistry · 2024Review
- Enhanced statistical sampling reveals microscopic complexity in the talin mechanosensor folding energy landscape.Nature physics · 2023Article
- Force-Dependent Folding Kinetics of Single Molecules with Multiple Intermediates and Pathways.The journal of physical chemistry letters · 2022Article
- Co-Translational Folding of Multi-Domain Proteins.Frontiers in molecular biosciences · 2022Review
- Force Dependence of Proteins' Transition State Position and the Bell-Evans Model.Nanomaterials (Basel, Switzerland) · 2021Article
- Co-translational folding of nascent polypeptides: Multi-layered mechanisms for the efficient biogenesis of functional proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021Article
- Optical manipulation: advances for biophotonics in the 21st century.Journal of biomedical optics · 2021Review
- Disorder in a two-domain neuronal CaCellular and molecular life sciences : CMLS · 2021Article
- Effects of Ligand Binding on the Energy Landscape of Acyl-CoA-Binding Protein.Biophysical journal · 2020Article
- Insight into the Folding and Dimerization Mechanisms of the N-Terminal Domain from Human TDP-43.International journal of molecular sciences · 2020Article
- Single-Molecule Studies of Protein Folding with Optical Tweezers.Annual review of biochemistry · 2020Review
- Optical Tweezers Exploring Neuroscience.Frontiers in bioengineering and biotechnology · 2020Review
- Energetic dependencies dictate folding mechanism in a complex protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding.Nature communications · 2019Article
- Bio-Molecular Applications of Recent Developments in Optical Tweezers.Biomolecules · 2019Review
- Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the relaxation rate of applied force, demonstrating an unprecedented real-time control over the free-energy landscape of a protein. Constant-force experiments in combination with hidden Markov analysis revealed the free-energy landscape of the misfolding transitions under both physiological and pathological calcium concentrations. Remarkably for a calcium sensor, we found that higher calcium concentrations increased the lifetimes of the misfolded conformations, slowing productive folding to the native state. We propose a rugged, multidimensional energy landscape for neuronal calcium sensor-1 and speculate on a direct link between protein misfolding and calcium dysregulation that could play a role in neurodegeneration.
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.