ArticleProceedings of the National Academy of Sciences of the United States of America2016
Knotting and unknotting of a protein in single molecule experiments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 95 citations in OpenAlex.
- Tied to Work: Topologically Knotted SPOUT Methyltransferases and UCH Deubiquitinases in Cellular Biochemistry.Journal of cellular biochemistry · 2026Review
- Tightly Knotted Enzymes Inhibit Protein-Protein Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Generating knotted polymer and protein structures by machine learning.Communications chemistry · 2026Article
- One-pot dual protein labeling for simultaneous mechanical and fluorescent readouts in optical tweezers.Protein science : a publication of the Protein Society · 2025Article
- Folding of a tandemly knotted protein: Evidence that a polypeptide chain can get out of deep kinetic traps.Protein science : a publication of the Protein Society · 2025Article
- Is There a Functional Role for the Knotted Topology in Protein UCH-L1?Journal of chemical information and modeling · 2024Article
- Folding a Molecular Strand into a Trefoil Knot of Single Handedness with Co(II)/Co(III) Chaperones.Journal of the American Chemical Society · 2024Article
- Mechanical scission of a knotted polymer.Nature chemistry · 2024Article
- Structure, dynamics, and stability of the smallest and most complex 7The Journal of biological chemistry · 2024Article
- De novo design of knotted tandem repeat proteins.Nature communications · 2023Article
- Effect of temperature and nucleotide on the binding of BiP chaperone to a protein substrate.Protein science : a publication of the Protein Society · 2023Article
- AlphaFold predicts novel human proteins with knots.Protein science : a publication of the Protein Society · 2023Article
- Temperature dependent mechanical unfolding and refolding of a protein studied by thermo-regulated optical tweezers.Biophysical journal · 2023Article
- Revealing Topological Barriers against Knot Untying in Thermal and Mechanical Protein Unfolding by Molecular Dynamics Simulations.Biomolecules · 2021Article
- Slipknotted and unknotted monovalent cation-proton antiporters evolved from a common ancestor.PLoS computational biology · 2021Article
- Mechanical strength of RNA knot in Zika virus protects against cellular defenses.Nature chemical biology · 2021Article
- Model systems for optical trapping: the physical basis and biological applications.Biophysical reviews · 2021Review
- Converging experimental and computational views of the knotting mechanism of a small knotted protein.Biophysical journal · 2021Article
- Tying up the Loose Ends: A Mathematically Knotted Protein.Frontiers in chemistry · 2021Article
- Effects of turn-structure on folding and entanglement in artificial molecular overhand knots.Chemical science · 2020Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spontaneous folding of a polypeptide chain into a knotted structure remains one of the most puzzling and fascinating features of protein folding. The folding of knotted proteins is on the timescale of minutes and thus hard to reproduce with atomistic simulations that have been able to reproduce features of ultrafast folding in great detail. Furthermore, it is generally not possible to control the topology of the unfolded state. Single-molecule force spectroscopy is an ideal tool for overcoming this problem: by variation of pulling directions, we controlled the knotting topology of the unfolded state of the 52-knotted protein ubiquitin C-terminal hydrolase isoenzyme L1 (UCH-L1) and have therefore been able to quantify the influence of knotting on its folding rate. Here, we provide direct evidence that a threading event associated with formation of either a 31 or 52 knot, or a step closely associated with it, significantly slows down the folding of UCH-L1. The results of the optical tweezers experiments highlight the complex nature of the folding pathway, many additional intermediate structures being detected that cannot be resolved by intrinsic fluorescence. Mechanical stretching of knotted proteins is also of importance for understanding the possible implications of knots in proteins for cellular degradation. Compared with a simple 31 knot, we measure a significantly larger size for the 52 knot in the unfolded state that can be further tightened with higher forces. Our results highlight the potential difficulties in degrading a 52 knot compared with a 31 knot.
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