ArticleProceedings of the National Academy of Sciences of the United States of America2016
Folding and assembly of the large molecular machine Hsp90 studied 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 35 papers.
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Who cites it
35 citing papers in PubMed.
- Direct single-molecule visualization of Hsp90-mediated relief of an Hsp70-folding block.Science advances · 2026Article
- Protocol for sample preparation and single-molecule optical tweezers study of nanodisc-embedded ABC transporter OpuA.STAR protocols · 2025Article
- Roquin exhibits opposing effects on RNA stem-loop stability through its two ROQ domain binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- One-pot dual protein labeling for simultaneous mechanical and fluorescent readouts in optical tweezers.Protein science : a publication of the Protein Society · 2025Article
- The known unknowns of the Hsp90 chaperone.eLife · 2024Review
- A Biophysics Toolbox for Reliable Data Acquisition and Processing in Integrated Force-Confocal Fluorescence Microscopy.ACS photonics · 2024Article
- The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments.Nature communications · 2023Article
- Single-molecule mechanical studies of chaperones and their clients.Biophysics reviews · 2022Review
- Using Optical Tweezers to Monitor Allosteric Signals Through Changes in Folding Energy Landscapes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Co-Translational Folding of Multi-Domain Proteins.Frontiers in molecular biosciences · 2022Review
- Classifying Residues in Mechanically Stable and Unstable Substructures Based on a Protein Sequence: The Case Study of the DnaK Hsp70 Chaperone.Nanomaterials (Basel, Switzerland) · 2021Article
- Article
- Facile tethering of stable and unstable proteins for optical tweezers experiments.Biophysical journal · 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 tweezers in single-molecule biophysics.Nature reviews. Methods primers · 2021Article
- Piecewise All-Atom SMD Simulations Reveal Key Secondary Structures in Luciferase Unfolding Pathway.Biophysical journal · 2020Article
- Studying heat shock proteins through single-molecule mechanical manipulation.Cell stress & chaperones · 2020Review
- Single-Molecule Studies of Protein Folding with Optical Tweezers.Annual review of biochemistry · 2020Review
- Review
- Simultaneous sensing and imaging of individual biomolecular complexes enabled by modular DNA-protein coupling.Communications chemistry · 2020Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Folding of small proteins often occurs in a two-state manner and is well understood both experimentally and theoretically. However, many proteins are much larger and often populate misfolded states, complicating their folding process significantly. Here we study the complete folding and assembly process of the 1,418 amino acid, dimeric chaperone Hsp90 using single-molecule optical tweezers. Although the isolated C-terminal domain shows two-state folding, we find that the isolated N-terminal as well as the middle domain populate ensembles of fast-forming, misfolded states. These intradomain misfolds slow down folding by an order of magnitude. Modeling folding as a competition between productive and misfolding pathways allows us to fully describe the folding kinetics. Beyond intradomain misfolding, folding of the full-length protein is further slowed by the formation of interdomain misfolds, suggesting that with growing chain lengths, such misfolds will dominate folding kinetics. Interestingly, we find that small stretching forces applied to the chain can accelerate folding by preventing the formation of cross-domain misfolding intermediates by leading the protein along productive pathways to the native state. The same effect is achieved by cotranslational folding at the ribosome in vivo.
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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.