ArticleProceedings of the National Academy of Sciences of the United States of America2007
Single-molecule force spectroscopy reveals a mechanically stable protein fold and the rational tuning of its mechanical stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Evolution of N-terminal mechanical lability as a determinant for Type III secretion.Protein science : a publication of the Protein Society · 2026Article
- Validation ofACS central science · 2026Article
- Single-molecule mechanostructural fingerprinting of nucleic acid conformations.Nucleic acids research · 2026Article
- A Type III secretion system effector evolved to be mechanically labile and initiate unfolding from the N-terminus.bioRxiv : the preprint server for biology · 2026Article
- Mechanochemistry: Fundamental Principles and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Structural constraints of pyocin S2 import through the ferripyoverdine receptor FpvAI.PNAS nexus · 2024Article
- Energy landscape of conformational changes for a single unmodified protein.Npj biosensing · 2024Article
- Tension-tuned receptors for synthetic mechanotransduction and intercellular force detection.Nature biotechnology · 2023Article
- A Method for Assessing the Robustness of Protein Structures by Randomizing Packing Interactions.Frontiers in molecular biosciences · 2022Article
- Force Dependence of Proteins' Transition State Position and the Bell-Evans Model.Nanomaterials (Basel, Switzerland) · 2021Article
- Protein folding mechanism revealed by single-molecule force spectroscopy experiments.Biophysics reports · 2021Article
- Structural Water Stabilizes Protein Motifs in Liquid Protein Phase: The Folding Mechanism of Short β-Sheets Coupled to Phase Transition.International journal of molecular sciences · 2021Article
- Mechanism for the Unfolding of the TOP7 Protein in Steered Molecular Dynamics Simulations as Revealed by Mutual Information Analysis.Frontiers in molecular biosciences · 2021Article
- Single molecule force spectroscopy reveals the context dependent folding pathway of the C-terminal fragment of Top7.Chemical science · 2020Article
- Mechanical Stability of a Small, Highly-Luminescent Engineered Protein NanoLuc.International journal of molecular sciences · 2020Article
- Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes.Frontiers in molecular biosciences · 2020Review
- Probing the Basis of α-Synuclein Aggregation by Comparing Simulations to Single-Molecule Experiments.Biophysical journal · 2019Article
- Removal of a Conserved Disulfide Bond Does Not Compromise Mechanical Stability of a VHH Antibody Complex.Nano letters · 2019Article
- Injectable dynamic covalent hydrogels of boronic acid polymers cross-linked by bioactive plant-derived polyphenols.Biomaterials science · 2018Article
- The influence of disulfide bonds on the mechanical stability of proteins is context dependent.The Journal of biological chemistry · 2017Article
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7 authors.
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Abstract
It is recognized that shear topology of two directly connected force-bearing terminal beta-strands is a common feature among the vast majority of mechanically stable proteins known so far. However, these proteins belong to only two distinct protein folds, Ig-like beta sandwich fold and beta-grasp fold, significantly hindering delineating molecular determinants of mechanical stability and rational tuning of mechanical properties. Here we combine single-molecule atomic force microscopy and steered molecular dynamics simulation to reveal that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (2003) Science 302:1364-1368] represents a mechanically stable protein fold that is distinct from Ig-like beta sandwich and beta-grasp folds. Although the two force-bearing beta strands of Top7 are not directly connected, Top7 displays significant mechanical stability, demonstrating that the direct connectivity of force-bearing beta strands in shear topology is not mandatory for mechanical stability. This finding broadens our understanding of the design of mechanically stable proteins and expands the protein fold space where mechanically stable proteins can be screened. Moreover, our results revealed a substructure-sliding mechanism for the mechanical unfolding of Top7 and the existence of two possible unfolding pathways with different height of energy barrier. Such insights enabled us to rationally tune the mechanical stability of Top7 by redesigning its mechanical unfolding pathway. Our study demonstrates that computational biology methods (including de novo design) offer great potential for designing proteins of defined topology to achieve significant and tunable mechanical properties in a rational and systematic fashion.
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