ArticleProceedings of the National Academy of Sciences of the United States of America2016
Force-dependent switch in protein unfolding pathways and transition-state movements.
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 28 papers.
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28 citing papers in PubMed.
- Force-Induced Ankle Opening Reveals Mechanical Stabilization of the Ankle of Human β-Cardiac Myosin.ACS nano · 2026Article
- Full-Length Context Disrupts Folding of IgG-Binding Domains of Protein A.bioRxiv : the preprint server for biology · 2025Article
- Heterogeneous folding landscapes and predetermined breaking points within a protein family.Protein science : a publication of the Protein Society · 2024Article
- A Hydrophobic Core Stabilizes the Residual Structure in the RRM2 Intermediate State of the ALS-linked Protein TDP-43.Journal of molecular biology · 2024Article
- Molecular mechanisms of catch bonds and their implications for platelet hemostasis.Biophysical reviews · 2023Review
- Catch bonds in sickle cell disease: Shear-enhanced adhesion of red blood cells to laminin.Biophysical journal · 2023Article
- Using steered molecular dynamic tension for assessing quality of computational protein structure models.Journal of computational chemistry · 2022Article
- On distributions of barrier crossing times as observed in single-molecule studies of biomolecules.Biophysical reports · 2021Article
- Conserved patterns and interactions in the unfolding transition state across SH3 domain structural homologues.Protein science : a publication of the Protein Society · 2021Article
- Diverse Folding Pathways of HIV-1 Protease Monomer on a Rugged Energy Landscape.Biophysical journal · 2019Article
- On the Interpretation of Force-Induced Unfolding Studies of Membrane Proteins Using Fast Simulations.Biophysical journal · 2019Article
- Multiplexed protein force spectroscopy reveals equilibrium protein folding dynamics and the low-force response of von Willebrand factor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mechanical unfolding of spectrin reveals a super-exponential dependence of unfolding rate on force.Scientific reports · 2019Article
- Using Single-Molecule Chemo-Mechanical Unfolding to Simultaneously Probe Multiple Structural Parameters in Protein Folding.Methods and protocols · 2019Article
- A small single-domain protein folds through the same pathway on and off the ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Unraveling the mechanism of the cadherin-catenin-actin catch bond.PLoS computational biology · 2018Article
- How Do We Know when Single-Molecule Force Spectroscopy Really Tests Single Bonds?Biophysical journal · 2018Review
- Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states.The Journal of chemical physics · 2018Article
- Impact of hydrodynamic interactions on protein folding rates depends on temperature.Physical review. E · 2018Article
- Transition Path Times Measured by Single-Molecule Spectroscopy.Journal of molecular biology · 2018Review
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Abstract
Although it is known that single-domain proteins fold and unfold by parallel pathways, demonstration of this expectation has been difficult to establish in experiments. Unfolding rate, [Formula: see text], as a function of force f, obtained in single-molecule pulling experiments on src SH3 domain, exhibits upward curvature on a [Formula: see text] plot. Similar observations were reported for other proteins for the unfolding rate [Formula: see text]. These findings imply unfolding in these single-domain proteins involves a switch in the pathway as f or [Formula: see text] is increased from a low to a high value. We provide a unified theory demonstrating that if [Formula: see text] as a function of a perturbation (f or [Formula: see text]) exhibits upward curvature then the underlying energy landscape must be strongly multidimensional. Using molecular simulations we provide a structural basis for the switch in the pathways and dramatic shifts in the transition-state ensemble (TSE) in src SH3 domain as f is increased. We show that a single-point mutation shifts the upward curvature in [Formula: see text] to a lower force, thus establishing the malleability of the underlying folding landscape. Our theory, applicable to any perturbation that affects the free energy of the protein linearly, readily explains movement in the TSE in a β-sandwich (I27) protein and single-chain monellin as the denaturant concentration is varied. We predict that in the force range accessible in laser optical tweezer experiments there should be a switch in the unfolding pathways in I27 or its mutants.
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