ArticleProceedings of the National Academy of Sciences of the United States of America2008
Atomic force microscopy reveals parallel mechanical unfolding pathways of T4 lysozyme: evidence for a kinetic partitioning mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Calpain small subunit homodimerization is robust and calcium-independent.FEBS letters · 2026Article
- Mechanical fatigue testing in silico: Dynamic evolution of material properties of nanoscale biological particles.Acta biomaterialia · 2023Article
- Single-molecule displacement assay reveals strong binding of polyvalent dendrimer ligands to telomeric G-quadruplex.Analytical biochemistry · 2022Article
- Structural and Kinetic Views of Molecular Chaperones in Multidomain Protein Folding.International journal of molecular sciences · 2022Review
- Protein folding mechanism revealed by single-molecule force spectroscopy experiments.Biophysics reports · 2021Article
- Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis.Nanomaterials (Basel, Switzerland) · 2021Article
- Mechanically tightening, untying and retying a protein trefoil knot by single-molecule force spectroscopy.Chemical science · 2020Article
- The Non-dominant AAA+ Ring in the ClpAP Protease Functions as an Anti-stalling Motor to Accelerate Protein Unfolding and Translocation.Cell reports · 2020Article
- Iterative annealing mechanism explains the functions of the GroEL and RNA chaperones.Protein science : a publication of the Protein Society · 2020Review
- Unraveling the Mechanical Unfolding Pathways of a Multidomain Protein: Phosphoglycerate Kinase.Biophysical journal · 2018Article
- Differences in the mechanical unfolding pathways of apo- and copper-bound azurins.Scientific reports · 2018Article
- Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein, Luciferase.Biophysical journal · 2017Article
- Structural Heterogeneity of CNGA1 Channels Revealed by Electrophysiology and Single-Molecule Force Spectroscopy.ACS omega · 2016Article
- How cooperative are protein folding and unfolding transitions?Protein science : a publication of the Protein Society · 2016Review
- Kinetic Ductility and Force-Spike Resistance of Proteins from Single-Molecule Force Spectroscopy.Biophysical journal · 2016Article
- A simple two-state protein unfolds mechanically via multiple heterogeneous pathways at single-molecule resolution.Nature communications · 2016Article
- The mechanochemistry of copper reports on the directionality of unfolding in model cupredoxin proteins.Nature communications · 2015Article
- Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.Nature communications · 2015Article
- Single-molecule chemo-mechanical unfolding reveals multiple transition state barriers in a small single-domain protein.Nature communications · 2015Article
- Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.F1000Research · 2015Article
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2 authors.
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Abstract
Kinetic partitioning is predicted to be a general mechanism for proteins to fold into their well defined native three-dimensional structure from unfolded states following multiple folding pathways. However, experimental evidence supporting this mechanism is still limited. By using single-molecule atomic force microscopy, here we report experimental evidence supporting the kinetic partitioning mechanism for mechanical unfolding of T4 lysozyme, a small protein composed of two subdomains. We observed that on stretching from its N and C termini, T4 lysozyme unfolds by multiple distinct unfolding pathways: the majority of T4 lysozymes unfold in an all-or-none fashion by overcoming a dominant unfolding kinetic barrier; and a small fraction of T4 lysozymes unfold in three-state fashion involving unfolding intermediate states. The three-state unfolding pathways do not follow well defined routes, instead they display variability and diversity in individual unfolding pathways. The unfolding intermediate states are local energy minima along the mechanical unfolding pathways and are likely to result from the residual structures present in the two subdomains after crossing the main unfolding barrier. These results provide direct evidence for the kinetic partitioning of the mechanical unfolding pathways of T4 lysozyme, and the complex unfolding behaviors reflect the stochastic nature of kinetic barrier rupture in mechanical unfolding processes. Our results demonstrate that single-molecule atomic force microscopy is an ideal tool to investigate the folding/unfolding dynamics of complex multimodule proteins that are otherwise difficult to study using traditional methods.
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