Mechanisms of Nanonewton Mechanostability in a Protein Complex Revealed by Molecular Dynamics Simulations and Single-Molecule Force Spectroscopy
Autor: | Zaida Luthey-Schulten, Constantin Schoeler, Ellis Durner, Michael A. Nash, Hermann E. Gaub, Edward A. Bayer, Klara H. Malinowska, Rafael C. Bernardi, Bruna Gregatti de Carvalho |
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Rok vydání: | 2019 |
Předmět: |
Chemistry
fungi Protein domain Force spectroscopy food and beverages A protein General Chemistry Molecular Dynamics Simulation 010402 general chemistry Microscopy Atomic Force 01 natural sciences Biochemistry Catalysis Article Single Molecule Imaging 0104 chemical sciences Molecular dynamics Colloid and Surface Chemistry Bacterial Proteins Ruminococcus Macromolecular Complexes Biophysics Molecule Function (biology) Mechanical Phenomena |
Zdroj: | Journal of the American Chemical Society |
ISSN: | 0002-7863 |
DOI: | 10.1021/jacs.9b06776 |
Popis: | Can molecular dynamics simulations predict the mechanical behavior of protein complexes? Can simulations decipher the role of protein domains of unknown function in large macromolecular complexes? Here, we employ a wide-sampling computational approach to demonstrate that molecular dynamics simulations, when carefully performed and combined with single-molecule atomic force spectroscopy experiments, can predict and explain the behavior of highly mechanostable protein complexes. As a test case, we studied a previously unreported homologue from; Ruminococcus flavefaciens; called X-module-Dockerin (XDoc) bound to its partner Cohesin (Coh). By performing dozens of short simulation replicas near the rupture event, and analyzing dynamic network fluctuations, we were able to generate large simulation statistics and directly compare them with experiments to uncover the mechanisms involved in mechanical stabilization. Our single-molecule force spectroscopy experiments show that the XDoc-Coh homologue complex withstands forces up to 1 nN at loading rates of 10; 5; pN/s. Our simulation results reveal that this remarkable mechanical stability is achieved by a protein architecture that directs molecular deformation along paths that run perpendicular to the pulling axis. The X-module was found to play a crucial role in shielding the adjacent protein complex from mechanical rupture. These mechanisms of protein mechanical stabilization have potential applications in biotechnology for the development of systems exhibiting shear enhanced adhesion or tunable mechanics. |
Databáze: | OpenAIRE |
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